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Biomedical subjects

J Tigges

Publications and source records attributed to J Tigges.

At least 19 recordsLinked to original sources
PubMed1999

The human B cell response to IL-13 is dependent on cellular phenotype as well as mode of activation.

Normal mature quiescent human B lymphocytes, isolated as a function of buoyant density, require activation for up-regulation of IL-13R constituents. Cell activation through a combination of surface Ig and CD40 receptor ligation leads to the most substantial message production for IL-13Ralpha1. Functional consequences of this receptor variation, in initially quiescent cells, includes demonstrable effects on cellular proliferation in response to ligand exposure. Variations in the method of surface activation, with particular emphasis on the CD40 receptor, reveals that immobilized CD40 ligand may be sufficient, in and of itself, to up-regulate IL-13Ralpha1, which may bear significance for B-lymphocyte bystander proliferation. Regulation of the IL-13Ralpha1 protein and message also differs as a function of cellular phenotype. Although values are greater in memory than naive B cells, as they are initially isolated from extirpated tonsils, variations in the magnitude of message and protein, as a function of surface stimulation, are more substantial in the naive subset. The magnitude of variation in message production in naive cells is associated with a more vigorous proliferative response to IL-13 than seen in memory lymphocytes. The cellular response to IL-13, as a function of activation and phenotype, is the converse of that demonstrated for IL-2. Evaluation of proliferation, receptor message, ligand binding protein production, and the response to putatively synergistic cytokines reveals that IL-2 is the predominant lymphokine utilized by memory cells. This is in contradistinction to IL-13, which along with IL-4, are the predominant moieties for naive lymphocytes.

B-Lymphocyte Subsets↗
PubMed1999

Brain weight throughout the life span of the chimpanzee.

Studies on human postmortem material report lower brain weights in older than in younger cohorts, whereas there is no apparent change with age in the rhesus monkey. In view of these contrasting results, we examined the pattern of brain weight across the life span in the chimpanzee, one of the closest biological relatives of humans. To place the study in context of the empirical life expectancy of the chimpanzee, we first performed a survival analysis on data from 275 chimpanzees that were maintained in the colony of the Yerkes Primate Center. The survival analysis revealed the maximum life spans of female and male chimpanzees to be about 59 and 45 years, respectively. We examined fresh brain weights from 76 chimpanzees ranging in age from birth to 59.4 years of age. The brains were taken from 9 infants (birth to 1 year of age), 25 juveniles (1-7 years), 13 adolescents (7-15 years), 21 young adults (15-30 years), and 8 old adults (over 30 years). Adult brain weight was achieved by the age of 7 years. The adolescent and young adult chimpanzees had the largest brain weights; in these two age groups combined, the mean brain weight (+/- standard deviation) was 368.1 g (+/-37.3) for females (n = 17) and 405.6 g (+/-39.4) for males (n = 17). This sex difference was statistically significant (P < 0.01). Simple linear regression performed on the combined material from females and males aged 7 years and older revealed a decline in brain weight with advancing age of 1.1 g/year (P < 0.05). When the effect of sex on brain weight was statistically controlled for, the loss of brain weight with age was 0.9 g/year (P = 0.07). These results suggest that brain weight declines moderately with age in the chimpanzee as it does in humans.

Age Factors↗
PubMed1997

Distribution of muscarinic cholinergic receptor proteins m1 to m4 in area 17 of normal and monocularly deprived rhesus monkeys.

Antibodies to muscarinic cholinergic receptor proteins m1 to m4 were used in striate cortex tissue of normal rhesus monkeys to determine the laminar distribution of these proteins with special attention to geniculorecipient layers. The normal patterns were compared to those of monkeys whose ocular dominance system had been altered by visual deprivation. In normal monkeys, immunoreactivity of all four proteins was localized in complex laminar patterns; m1 was densest in layers 2, 3, and 6, followed by layer 5. In contrast, m2 reactivity was densest in lower layer 4C and in 4A; the latter exhibited a honeycomb pattern. Layers 2 and 3 displayed alternating dense and light regions; this pattern was complementary to that of cytochrome oxidase (CytOx). Laminar immunoreactivity for the m3 receptor was similar to the CytOx pattern, including a honeycomb in 4A and a pattern of alternating darker and lighter patches in layers 2/3. Antibody to m4 reacted most densely with layers 1, 2, 3, and 5, layers 2 and 3 exhibited alternating dark and light regions, and layer 4A had a faint honeycomb. Layer 4C was the lightest band. The differential distribution of these four muscarinic receptor subtypes suggests distinct roles in cholinergic modulation of visual processing in the primate striate cortex. Furthermore, all four muscarinic receptors appear to be insensitive to elimination of visual input via monocular occlusion from birth, to deprivation of pattern vision in one eye during a specific time period in adulthood, and to long-term retinal injury.

Animals↗
PubMed1997

Neuropeptide Y in the infundibular nucleus and hypophysis of great apes.

We studied the distribution of neuropeptide Y (NPY) immunoreactivity in the infundibular nucleus and the hypophysis of the chimpanzee, gorilla, and orangutan. Using antibodies developed in rabbit against synthetic porcine NPY, we found numerous NPY-immunoreactive neuronal somata in the infundibular nucleus; this nucleus was also filled with short NPY-positive processes and an abundance of punctate structures that could be indicative of synaptic terminals. Numerous varicose NPY-positive fibers were concentrated in the upper infundibular stem in association with capillary loops of the portal vasculature and with the long portal vessels. Bundles of long varicose fibers ran down the infundibular stem, some appearing to terminate in the lower stem in the vicinity of short portal vessels. The bulbous infundibular process contained only sparsely distributed fibers; they were mostly concentrated near vessels at the border between the infundibular process and the anterior pituitary gland, where the fibers often terminated in a spray-like fashion near blood vessels. No NPY immunoreactivity was seen in the anterior pituitary gland. These results provide anatomical evidence for the release of NPY into the portal vasculature of great apes.

Animals↗
PubMed1997

Markers of platelet activation and oxidant stress in atherothrombotic disease.

Several new approaches to the study of platelet activation have been developed. Logically, these should be combined with novel indices of coagulant function (60,61) to select rational targets for antithrombotic drugs. They may also be invaluable in dose-finding, which has been a particular weakness in this area of drug development (62,63). While activation of platelets and the coagulation cascade are virtually simultaneous events, markers of the atherosclerosis are also artificially segregated from those of the complicating thrombotic process. Oxidant stress has been implicated in both platelet activation (64) and atherogenesis (65), yet our ability to study this system has been so constrained that we are unsure of appropriate doses of antioxidant vitamins. Novel approaches to this problem promise the ability to study oxidative modification of proteins (46,66,67), lipids (57) and DNA (45,68) in clinical studies.

Arteriosclerosis↗
PubMed1996

Neurobiological bases of age-related cognitive decline in the rhesus monkey.

The rhesus monkey offers a useful model of normal human aging because when monkeys are tested on a battery of behavioral tasks that can also be used to evaluate cognition in humans, it is found that the monkeys undergo an age-related decline in several domains of cognitive function as do humans. In monkeys these changes begin at about 20 years of age. To determine what gives rise to this cognitive decline, we have examined several parameters in the brains of monkeys. Some parameters do not change with age. Examples of this are the numbers of neurons in the neocortex and hippocampal formation, and the numbers of synapses in the hippocampal formation. Changes in other parameters can be positively correlated with chronological age; examples of this are numbers of neuritic plaques, a decrease in the numbers of neurons in the striatally projecting pars compacta of the substantia nigra, and a decrease in the thickness of layer I in primary visual cortex. But the most interesting changes are those that correlate either with cognitive decline alone, or with both cognitive decline and chronological age. Among these are a breakdown in the integrity of myelin around axons, an overall reduction in the volume of white matter in the cerebral hemispheres, thinning of layer I in area 46 of prefrontal cortex, and decreases in the cell density in cortically projecting brain stem nuclei. To date then, our studies suggest that the cognitive declines evident in the rhesus monkey may be a consequence of changes in layer I and in the integrity of myelinated axons, rather than an age-related loss of cortical neurons or synapses, as has long been assumed.

Aging↗
PubMed1996

Preservation into old age of synaptic number and size in the supragranular layer of the dentate gyrus in rhesus monkeys.

In order to determine whether there are age-related changes in the supragranular layer of the dentate gyrus of the rhesus monkey, we examined this layer in monkeys 4-35 years of age, spanning the entire range of adulthood of this species. Electron microscopic analyses were conducted to determine whether there is an age-related change in the number of synapsing axon terminals, in the cross-sectional area of these terminals, or in the length of the postsynaptic density at the synaptic junction. Only asymmetrical synapses in the anterior dentate gyrus were evaluated. In a subset of our monkeys (n = 6, ages 4-31 years), we compared three different approaches to the estimation of synaptic density: (1) the conventional profile method, in which synapse numbers are expressed per unit area of the examined tissue section; (2) the empirical formula of Colonnier and Beaulieu for converting areal densities into number of synapses per unit volume, and (3) the 'disector' method, a stereological approach to the estimation of the number of synapses per unit volume that makes no assumption about the shape of the objects. Data are presented validating the small-fold method of estimating section thickness for the disector. The three methods were highly intercorrelated (rs approximately 0.89), and none of the methods revealed an age-related loss of synapses. Analysis of the thickness of the dentate gyrus molecular layer suggests that the reference volume in which these synapses were counted dose not change with age. In addition, the conventional profile method showed no age-related change in the number of axodendritic or axospinous synapses, the cross-sectional area of the synapsing terminals, or the length of the postsynaptic densities of synapses. Together, these data suggest a remarkable age-related preservation of synapses in the normal aging monkey.

Aging↗
PubMed1995

Sources of subcortical afferents to the macaque's dorsal lateral geniculate nucleus.

BACKGROUND: The dorsal lateral geniculate nucleus (dLGN) is the thalamic region responsible for transmitting retina signals to cortex. Brainstem pathways to this nucleus have been described in several species and are believed to control the retinocortical pathway depending on the state of the animal (awake, asleep, drowsy, etc.). The purpose of this study was to determine all of the subcortical sources of afferents to the dLGN in a higher primate, the macaque monkey, whose visual system is similar to that of humans. METHODS: Injections of horseradish peroxidase (HRP), with or without conjugation to wheat germ agglutinin, were made into the dLGNs of seven macaque monkeys, followed by perfusion, brain sectioning, and analyses of neurons in the brainstem, thalamus, and hypothalamus that contained the retrogradely transported marker. RESULTS: The reticular nucleus of the thalamus, pedunculopontine nucleus, parabigeminal nucleus, pretectal nucleus of the optic tract, superior colliculus, dorsal raphe nucleus, and tuberomammillary region of the hypothalamus contained many retrogradely labeled neurons ipsilateral to the injections. In the contralateral brainstem, HRP-labeled cells were found only in the pedunculopontine nucleus, nucleus of the optic tract, and dorsal raphe nucleus. The number of labeled neurons on the contralateral side was about one-half of that in corresponding ipsilateral nuclei. The locus coeruleus contained no labeled neurons in four of the macaques that had injections limited to the dLGN. CONCLUSION: There are seven subcortical regions that send afferents to the dLGNs of macaque monkeys. Except for the locus coeruleus, these are the same as observed for other species, such as the cat and rat, and indicate the possible sources of subcortical control over the dLGNs of humans.

Animals↗
PubMed1995

Mild age-related changes in the dentate gyrus of adult rhesus monkeys.

Memory and cognitive performance decline with advancing age in humans. Rhesus monkeys show a similar age-related memory deficit. Since the functional neuroanatomy of the temporal lobes in the two species is similar, and since the circuits of the temporal lobes are known to be involved in memory function, we undertook a study of the anatomical characteristics of synapses in the dentate gyrus of the rhesus monkey throughout the adult life span. Light- and electron-microscopic examinations were carried out on the dentate gyrus of 10 adult rhesus monkeys (4-35 years) to determine the effect of age on the thickness of the molecular layer and on axon terminals in the outer portion of the molecular layer. The thickness measurements were made on 100-microns-thick Vibratome sections and on 1 micron-thick Araldite-embedded sections. A total of 100 electron micrographs covering a test area of 3,600 microns2 for each monkey were taken in the outer portion of the molecular layer. Counts of axon terminals synapsing with dendritic spines or shafts, measurements of the cross-sectional area of these terminals, and the length of the postsynaptic density were taken on enlarged prints. The thickness of the molecular layer remained unchanged throughout adulthood. Statistical analysis revealed no overall age-associated loss of synapsing axon terminals or shrinkage of the cross-sectional areas of their profiles. Further, there was no loss in the total number of synapses (axospinous plus axodendritic) or any change in the lengths of their postsynaptic membrane densities. However, when axodendritic (shaft) synapses (which constitute 13% of the total) were considered separately, a statistically significant age-related loss was detected. Qualitative observations revealed that older monkeys had a moderate number of dystrophic myelinated axons and corpora amylacea located in astrocytic processes in the outer portion of the molecular layer, features not present in young monkeys. Also, glial cells and pericytes showed age-associated accumulation of lipofuscin-like inclusions. A single occurrence of a structured inclusion body in a dendrite was observed in a 10-year-old monkey. In conclusion, most synaptic measures in the dentate gyrus remain stable throughout adulthood of rhesus monkey and there are relatively few other age-related changes. The small age-associated loss of axodendritic synapses is only apparent following separate statistical treatment of these synapses. The functional significance of this loss is unclear since it would result in only 3% reduction in total synapses (shaft plus spinous) from 4 to 35 years of age, the maximal life span of the rhesus monkey.

Aging↗
PubMed1994

Neuropathology and apolipoprotein E profile of aged chimpanzees: implications for Alzheimer disease.

Neuropathological findings in three aged chimpanzees were compared with those in rhesus monkeys and individuals with Alzheimer disease. Senile plaques and blood vessels were immunoreactive for amyloid beta-protein and apolipoprotein E (apoE) in the nonhuman primates, recapitulating findings in human aging and Alzheimer disease. Neurofibrillary tangles, another hallmark of Alzheimer disease, were absent. PCR/restriction-enzyme analysis in chimpanzees revealed an APOE profile similar to the human APOE type 4 allele associated with an increased risk of Alzheimer disease. These findings militate against the hypothesis that the absence of APOE type 3 allele predisposes to neurofibrillary tangle formation and support the value of aged primates for exploring mechanisms of amyloid processing and the role of apoE.

Aging↗
PubMed1994

Apolipoprotein E4 and beta amyloid in senile plaques and cerebral blood vessels of aged rhesus monkeys.

Recent studies of late onset familial and sporadic Alzheimer's disease (AD) show a genetic disequilibrium between inheritance of the epsilon 4 allele of the apolipoprotein E (ApoE) gene and development of AD. beta-Amyloid (A beta)-positive senile plaques and blood vessels in AD are immunoreactive for ApoE, suggesting that ApoE plays a role in amyloid deposition. We examined the brains of nine rhesus monkeys (Macaca mulatta) to determine the immunohistochemical distribution of ApoE and to investigate the association of ApoE with A beta in this species. Antibodies to ApoE and A beta labeled senile plaques and vessels in the brains of aged monkeys, indicating cross-species homogeneity of the association of these two proteins. Polymerase chain reaction/restriction enzyme analysis of the ApoE epsilon 3/epsilon 4 allelic site (residue 112) in the rhesus monkey revealed that the rhesus has an arginine at this site like the human epsilon 4 allele, the cynomolgus monkey, baboon, cow, pig, mouse, and rat but unlike the human epsilon 3 allele and the rabbit. These results emphasize the value of aged nonhuman primates as animal models for A beta deposition and ApoE4-A beta interactions in AD and aging.

Aging↗
PubMed1992

Competition between an aphakic and an occluded eye for territory in striate cortex of developing rhesus monkeys: cytochrome oxidase histochemistry in layer 4C.

Monkey models were used to examine the effects of competition for cortical territory between two eyes which were deprived simultaneously, but each eye experienced a different type of deprivation. We wanted to determine whether, under this condition of binocular unequal deprivation, the postnatal process of segregation into ocular dominance columns proceeds according to the same rules as those that apply to competition between a deprived and an undeprived fellow eye. Our models involved surgical removal of the natural lens from one eye in newborn rhesus monkeys. The resulting aphakia was corrected optically to a near point with extended-wear contact lenses. The fellow eyes were either left unmanipulated or occluded with opaque contact lenses for varying periods during the day. At the end of the rearing period, some monkeys from each experimental group had either one eye enucleated or sustained injury to the retinal ganglion cells of one eye. The histochemical reaction for cytochrome oxidase was used to reveal the widths of ocular dominance columns in layer 4C of striate cortex in these monkeys. Under all experimental conditions, the axons related to the two eyes occupied segregated fields. The amount of cortical territory related to the aphakic, optically corrected eye depended on the manipulations of the fellow eye. In competition with an unmanipulated fellow eye, the aphakic eye's territory was greatly reduced. In competition with a part-time occluded eye, its territory was reduced to a lesser degree, depending on the duration of the occlusion. In competition with a continuously occluded eye, however, the space related to the aphakic, optically corrected eye was slightly greater than that related to the occluded eye. Since neither the aphakic nor the continuously occluded eye receives normal visual input, they are both impaired. Therefore, they may compete on an almost equal basis for synaptic territory in layer 4C of striate cortex. Moreover, it is likely that activities originating in the aphakic and the continuously occluded eye are asynchronous, and that this condition is sufficient to drive the postnatal segregation of inputs from the two deprived eyes.

Aging↗
PubMed1992

Axon terminals on Betz cell somata of area 4 in rhesus monkey throughout adulthood.

Previous work in our laboratory demonstrated an age-related decline in the size of Betz cell somata in cortical area 4 of the adult rhesus monkey brain. The present study was conducted to determine whether changes might also occur in the axon terminals upon these cortical cells. Tissue from area 4 was collected from seven rhesus monkeys and prepared for electron microscopy. The ages of the monkeys ranged from 5 to 35 years, covering the entire adult life span of this species. A total of 140 Betz cell profiles (20 per monkey) were examined. Measurements of these profiles confirmed our earlier finding of a decline in the perimeters of Betz cell somata with advancing age. The 1,540 axon terminals upon these cells, however, remained unchanged in size and length of membrane apposition, as well as in their number of mitochondria throughout the adult life (greater than or equal to 5 years) of the rhesus monkey. In addition, the total number of axon terminals on Betz cells did not change with age. Because the axosomatic terminals showed no age-associated changes, the material was used to calculate parametric characteristics of Betz cells and associated terminals. Betz cell somata of the rhesus monkey were estimated to have a mean membrane surface area of 5,700 microns2. Axosomatic terminals on Betz cell somata had a mean appositional area of about 3.33 microns2 and covered about 15% of the somal surface. Thus, on average, each Betz cell appeared to receive approximately 260 axosomatic terminals. There were also some conspicuous age-associated changes in the motor cortex that were not quantified. These included an accumulation of lipofuscin and the presence of a novel inclusion body in the somata of Betz cells. Age-related occurrences in the neuropil included the degeneration of axons and their myelin, membrane-bound holes, and neuritic (senile) plaques.

Aging↗
PubMed1992

Novel inclusion bodies in Betz cells of cortical area 4 of aged rhesus monkeys.

Seven adult rhesus monkeys ranging in age from 5 to 35 years were studied in an ultrastructural investigation of cortical area 4. Some Betz cells of layer 5 contained a perikaryal inclusion body (IB) of a unique and characteristic ultrastructural configuration that has not previously been described. The IBs consist of a regular array of three sets of equidistant parallel sheets and are not membrane bound. The distance between the sheets measures approximately 80 nm. The three sets of sheets intersect at an invariable angle of 60 degrees, forming a regular geometric structure. Each sheet comprises a single layer of parallel and densely packed straight filaments, which are approximately 10 nm thick. Thus the IBs present highly ordered crystalline arrays of filaments. The occurrence and number of IBs may be age related, since they appeared only in monkeys in mid to late adulthood and were most numerous in the oldest monkey.

Aging↗
PubMed1991

Parvalbumin immunoreactivity of the lateral geniculate nucleus in adult rhesus monkeys after monocular eye enucleation.

Immunocytochemical methods with antiserum to the calcium-binding protein parvalbumin (PV) were used to examine the effects of monocular enucleation on parvalbuminergic neurons and processes in the lateral geniculate nucleus (LGN) of adult rhesus monkeys. In the LGN of normal monkeys, numerous PV-positive neurons, including the largest neurons in the nucleus, and many PV-positive processes occur in all six laminae. After monocular enucleation, PV immunoreactivity is reduced in the neuropil of the denervated laminae compared to adjacent nondenervated and to normal laminae. PV immunoreactivity of somata in denervated laminae, however, appears to be indistinguishable from that of somata in nondenervated laminae, although neurons in the denervated laminae are smaller in size. Since LGN neurons in denervated laminae have lost their visual input, the functional role of PV in this nucleus may not relate directly to visual information processing.

Animals↗
PubMed1991

Effects of aphakia on the geniculostriate system of infant rhesus monkeys.

The effects on the visual system of rearing rhesus monkeys with monocular aphakia, corrected with extended-wear contact lenses, were assessed with anatomical, electrophysiological and behavioral methods. The major finding was that the effects of the various treatments on the aphakic eye varied in degree depending upon the amount of focused pattern input received by the aphakic eye compared to its fellow eye. The behavioral, electrophysiological and anatomical assessments of the treatment effects on the aphakic eyes correlated closely with each other. Because this experimental paradigm is similar to current clinical procedures for treating human infantile monocular cataracts, it provides a nonhuman primate model for studying aphakia.

Animals↗
PubMed1990

Termination of thalamic intralaminar nuclei afferents in visual cortex of squirrel monkey.

The projection of the thalamic intralaminar nuclei (ILN) upon the visual cortex in the squirrel monkey was studied using anterograde, autoradiographic techniques. In area 17, the ILN afferents terminate in the inner and outer portions of lamina V, whereas in areas 18 and 19 the fibers terminate more diffusely along the laminae V-VI boundary. Widespread labeling of layer I is seen throughout the occipital cortex.

Afferent Pathways↗