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Biomedical subjects

A Hendrickson

Publications and source records attributed to A Hendrickson.

At least 37 records · Page 2Linked to original sources

A morphological comparison of foveal development in man and monkey.

The fovea can first be identified in both monkey and human retina at 26-30% gestation as a region containing all adult retinal layers and only cone photoreceptors. A shallow foveal pit and cone outer segments appear by 63-65% gestation in both species. Prenatal development continues rapidly in the monkey, so that by birth a single layer of inner retinal neurons are present in the fovea, cones are three cells deep, inner segments are elongated, and outer segments are up to 50% of inner segment length. In contrast, human fovea does not reach a similar stage until several months after birth. The fovea is adult-like in monkey at 12 weeks and in human at 11-15 months, although human will mature further up to four to five years. This study shows that human fovea is less mature at birth than monkey but develops rapidly in infancy, suggesting that it may be even more susceptible to postnatal environmental influences than the commonly-used monkey model.

Anatomy, Comparative↗

Characterization of Vicia villosa agglutinin-labeled GABAergic interneurons in the hippocampal formation and in acutely dissociated hippocampus.

The distribution, morphology, and ionic conductances of Vicia villosa agglutinin (VVA)-labeled cells were examined in the rat hippocampal formation. The heaviest labeling and highest density of labeled neurons were found in the subicular complex. Lighter VVA-labeling and fewer labeled cells were found in hippocampal strata pyramidale, oriens, and alveus. VVA-labeled cells were found to be heterogeneous morphologically, including multipolar, bipolar, and basket-like shapes. The majority of VVA-labeled cells contained GABA and parvalbumin immunoreactivity; thus VVA-labeled cells in the hippocampal formation resemble previously described VVA-labeled neurons in cerebral cortex. Electrophysiological properties of subicular VVA-labeled cells were studied in an acutely dissociated neuron preparation. Dissociated cells were labeled in vitro with VVA coupled either to a fluorescent marker or to small beads. The viability of labeled dissociated cells was confirmed, and identified cells were partially characterized electrophysiologically using whole-cell voltage clamp recording. VVA-labeled cells were electrophysiologically similar to pyramidal cells from the same region, except that the VVA-labeled cells showed only small transient outward currents.

Animals↗

Pre- and postnatal development of GABA receptors in Macaca monkey visual cortex.

GABA is a putative inhibitory neurotransmitter in adult mammalian visual cortex but also has been implicated as playing a crucial role in cortical information processing during development. In order to understand better the role of GABA during primate visual cortex development, we have examined the time course of GABAA and GABAB receptor ontogenesis in 18 Macaca nemestrina monkeys ranging from fetal day 61 (F61d) to adulthood. The GABA and benzodiazepine binding sites of the GABAA receptor were detected by 3H-muscimol (3H-MS) and 3H-flunitrazepam (3H-FZ), respectively. GABAB receptors were detected by 3H-baclofen (3H-BA). All ligands were visualized by in vitro autoradiography. Quantitative analysis of film density was done to compare laminar changes during pre- and postnatal development. Saturation binding experiments were done for MS and FZ binding sites to determine receptor number (Bmax) and affinity (Kd) at selected pre- and postnatal ages. Both MS and FZ binding sites were present at F61d-72d throughout the cortical plate and marginal zone. FZ binding sites were more dense than MS binding sites over the cortical plate at young ages and were especially dense over the marginal zone. FZ binding sites also were present in lesser amounts over the subplate and intermediate zone, but not over the subventricular zone. By F119d-126d, layer 4 could be distinguished by its higher density for both ligands. The basic adult laminar pattern was established for both MS and BZ binding sites by birth (birth = F165d-170d). After birth, MS density increases dramatically in all layers, but layer 4C remains most dense to adulthood. FZ labeling is heavy in both layers 4 and 3 at birth but after 4 weeks after birth (P4 wk) it declines somewhat in the supragranular layers so that layer 4C now predominates. Labeling in layers 5/6 virtually disappears after birth. BA binding sites were present at F126d, at which time layer 4 was slightly lighter than the remainder of striate cortex; this laminar pattern remained basically the same throughout our series to adulthood. Competitive binding of agonist and antagonists for the GABAA receptor showed that MS binding characteristics were similar at F126d and P8.5 years (yr). MS binding site Bmax was about 8% of adult values at F72d, 24% by F126d, and 56% at F152d. Bmax then rose rapidly after birth to peak at P18wk at 169% of adult values, and then declined to P1yr. A second peak of 143% was found around P3.5yr, with adult values reached by P8.5yr.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗

Selective effects of experimental glaucoma on axonal transport by retinal ganglion cells to the dorsal lateral geniculate nucleus.

Rapid-phase axonal transport to the dorsal lateral geniculate nucleus (dLGN) was determined autoradiographically in seven macaque monkey eyes with chronic intraocular pressure (IOP) elevation, in four eyes with an acute IOP elevation, and in three eyes with normal IOP. The monkeys with chronic IOP elevation showed a greater decrease in radioactive labeling of the magnocellular layers of the dLGN than the parvocellular layers by qualitative examination. Grain counts in selected specimens confirmed that transport to the magnocellular layers was less than to the parvocellular layers in monkeys with chronic IOP elevation. This selectivity was present in mildly damaged specimens and increased with greater ganglion cell loss. In monkeys with acute IOP elevation, qualitative evaluation suggested no consistent difference in transport among the dLGN layers; one animal in this group had less transport to the parvocellular than to the magnocellular layers by grain counts. Starting in early stages of the disease, chronic experimental glaucoma causes preferential damage to the ganglion cells that project to the magnocellular layers of the dLGN.

Animals↗

High-dose melphalan and granulocyte-macrophage colony-stimulating factor for refractory multiple myeloma.

High-dose melphalan has induced remissions in about 40% of patients with refractory myeloma, but the mortality has been high, at about 20%, due to complications of prolonged granulocytopenia. In an attempt to stimulate earlier granulocyte recovery, recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) was administered subcutaneously to 23 patients with refractory myeloma who had been treated with melphalan at a high dose of 100 mg/m2. Thirty-nine percent of patients achieved marked tumor cytoreduction by at least 75%, 2 died within 2 months from infectious complications during severe neutropenia; and median durations of relapse-free and overall survival were 7 and 10+ months, respectively. The nine patients presenting with both advanced age over 50 years and a long history of prior therapy of over 1 year required significantly longer median times of 31 days for granulocytes and of 63 days for platelets to reach safe levels of at least 500/microL and 50,000/microL, respectively, than the 14 remaining patients who had none or only one of these adverse features (21 and 26 days, respectively). In a historic control of 43 patients treated previously with high-dose melphalan but without GM-CSF, hematologic recovery to the aforementioned levels of granulocytes and platelets proceeded over almost 5 weeks, regardless of age and prior treatment exposure. Thus GM-CSF seems to hasten marrow recovery, especially in patients with adequate normal marrow stem-cell reserve as defined by younger age or less prior therapy. While not shortening the duration of neutropenia, GM-CSF dose increments (from 0.25 to 0.5 to 0.75 mg/m2) increased the incidence of severe toxicity from 0% to almost 40%, especially among older patients. These results support the usefulness of low-dose GM-CSF (0.25 mg/m2) in stimulating marrow recovery in selected patients with adequate marrow reserve treated with high-dose melphalan for refractory multiple myeloma.

Colony-Stimulating Factors↗

A qualitative and quantitative analysis of the human fovea during development.

The anatomical development of the human fovea has been sampled from 22 weeks gestation to adulthood, using both qualitative and quantitative methods. The foveal depression continues to deepen after birth until 15 months, due to the migration of the cells of the inner retina toward the periphery. Before birth the rod-free zone or foveola is over 1000 microns in diameter, but it becomes progressively narrower after birth because of a centralward migration of cones. It reaches the adult diameter of 650-700 microns by 45 months of age. Postnatally, foveolar cone development is characterized by maturation, elongation, and an increase in packing density. Foveolar cone diameter changes markedly after birth, going from 7.5 microns at 5 days postnatal to 2 microns by 45 months. During this time the foveolar cone develops both its outer segment and basal axon process (fiber of Henle). This combination of elongation and centralward migration results in an increase of foveolar cone density from 18 cones/100 microns at 1 week postnatal to 42 cones/100 microns in the adult. Measures of foveola width and cone diameter reach the adult stage of development at 45 months of age, but the two important visual factors of outer segment length and cone packing density still are only half the adult values at 45 months of age.

Adult↗

Colocalization of [3H]muscimol and antisera to GABA and glutamic acid decarboxylase within the same neurons in monkey retina.

Two procedures have been used to test for the colocalization of different neuroanatomical gamma-aminobutyric acid (GABA)ergic markers within the same neurons in primate retina. First, sequential immunocytochemical processing of sections was done using antisera to glutamic acid decarboxylase and to GABA, and these antisera were visualized by peroxidase-antiperoxidase and fluorescein isothiocyanate techniques respectively. Colocalization of both antisera was found within the same neuron cell bodies. In the second experiment, immunocytochemical staining using GABA antiserum was performed on retinal tissue that had been previously incubated in vitro for neuronal uptake of [3H]muscimol. Both markers colocalized in 70% of the labeled cell body population.

Animals↗

Indoleamine-accumulating horizontal cells in the squirrel monkey retina.

Horizontal cells capable of selectively accumulating indoleamines have been found in the retina of Saimiri sciureus, the New World squirrel monkey. The uptake of 3H-serotonin (5HT) in vivo and in vitro has been localized by light and electron microscopic (EM) autoradiography only to horizontal cells. In the central retina up to 50% and in the periphery 15-20% of the somas lying at the scleral border of the inner nuclear layer are labeled. In EM autoradiographs, labeled processes occur as lateral elements in both cone and rod synaptic invaginations, but grain counts show four times as many rods as cones are labeled. The light-dark adaptational state of the retina has no apparent effect on 3H-5HT uptake, but it is temperature dependent, and is saturable as indicated by its inhibition in the presence of an excess of nonradioactive 5HT. The indoleamine-accumulating capacity of this population of horizontal cells also was demonstrated by histofluorescence microscopy. A single row of fluorescent cells with a round soma was found lying at the outer edge of the inner nuclear layer. These cells send fluorescent processes only into the outer plexiform layer. The authors suggest that 5HT is not the native transmitter of these squirrel monkey horizontal cells because they lack intrinsic fluorescence and only could be visualized after uptake of extrinsically applied indoleamines. The true transmitter is likely to be a closely related but nonfluorescent indole.

Animals↗

Overlap of retinal and prestriate cortical pathways in the primate pretectum.

Connections between the pretectum and prestriate visual cortex were examined following injection of HRP into area V4 of Macaca nemestrina monkeys. Orthograde label was found in nucleus olivarius (NO) and the sublenticular (SL) regions while retrogradely labeled neurons were present in the nucleus of the optic tract (NOT). Following injection of [3H]proline into one eye, 3 pretectal zones of retinal input were seen: NO, SL and the posterior pretectal region (PPR). These results indicate that NO and SL may be sites for retinal and cortical pathway interaction in primate pretectum.

Animals↗

The retina of the newborn human infant.

We have examined a pair of eyes from a normal, full-term infant who died at 8 days as a result of accidental injury. Eyes were obtained immediately after death, fixed, and sectioned for light microscopy. Results from both eyes were substantially the same. The macular region was still drastically immature at 1 week. Even though a foveal depression existed, all cell layers were still present across it. Furthermore, the inner nuclear layer was divided into two separate layers. The receptor layer was reduced to one or two cells thick; receptors had both inner and outer segments, but they were very short and stumpy. The region of immaturity covered about 5 degrees of the retina. These findings suggest that the central region of a human infant's retina is probably not fully functional at birth.

Humans↗

Hypertrophy of neurons in dorsal lateral geniculate nucleus following striate cortex lesions in infant monkeys.

Monkeys whose left striate cortex had been removed in infancy received bilateral injections of horseradish peroxidase (HRP) into the prelunate gyrus (PLG) prestriate cortex. Scattered large neurons in the dorsal lateral geniculate nucleus were retrogradely labeled in both hemispheres. On the lesioned side, the HRP-labeled cell bodies were 58% larger in area, showing an overall increase in soma size and complexity of dendritic field, suggesting a hypertrophy of the geniculate-PLG pathway following a neonatal striate cortex lesion.

Animals↗

Alterations of retinal inputs following striate cortex removal in adult monkey.

The morphology of the retina and central retino-recipient nuclei was studied in two monkeys that had undergone total bilateral striate cortex removal as adults. These animals had been behaviorally tested for two years after lesioning and had demonstrated significant recovery of pattern vision. Light and electron microscopy and autoradiography were done on the central retino-recipient nuclei following a monocular intravitreal injection of 3H-proline. Light microscopic analysis of retinal ganglion cell number showed a 30% loss in the parafoveal retina due to retrograde trans-synaptic degeneration. The most striking central change in retinal axon distribution was in the dorsal lateral geniculate nucleus (dLGN) where the parvocellular but not the magnocellular region showed a marked reduction in retinal input. Despite the loss of almost all dLGN neurons through retrograde degeneration, at the EM level both parvocellular and magnocellular regions contained islands of neuropil made up of retinal and several other types of synaptic terminals as well as small dendrites and pale unidentified processes. Approximately equal numbers of retinal terminals were identified by EM autoradiography in both regions of dLGN, which did not explain the apparent differences in labeling between the two regions seen in the light microscope. A second change in central retinal pathways was found in the olivary pretectal nucleus where a significant loss of retinal input also occurred. A third change, but in the opposite direction, was found in the pregeniculate nucleus (PGN) where the area of retinal terminals appeared enlarged. The remaining central retino-recipient nuclei had the same distribution of retinal input as the control animals.

Animals↗

Localization of substance P-like immunoreactivity within the monkey retina.

Substance P (SP)--like immunoreactivity has been localized to distinct retinal cell populations in the primate Macaca nemestrina by means of immunohistochemical techniques with a well-characterized monoclonal antiserum directed to SP. The specificity of the immunoreactive staining was established by absorption of the antiserum with 10 micro M synthetic SP. Specific SP-like immunoreactivity was observed within varicose processes located in the outer plexiform layer, inner nuclear layer (INL), and in three bands within the inner plexiform layer (IPL). SP-immunoreactive somata were located in the proximal INL, IPL, and ganglion cell layer. These studies have thus identified SP-containing amacrine cells, interstitial amacrine cells, and displayed amacrine cells. In addition, these studies suggest the existence of SP-containing interplexiform cells and perhaps ganglion cells.

Animals↗

Anisometropic amblyopia in Macaca nemestrina monkeys produced by atropinization of one eye during development.

Two macaque monkeys were reared with daily administration of the cycloplegic drug, atropine, to one eye until 8 months after birth. Behavioral testing of contrast sensitivity functions in the atropinized eyes during the rearing period demonstrated that this rearing procedure caused the treated eyes to be chronically defocused. Measurement at the age of 6 or 8 months of contrast sensitivity while optically correcting the defocus demonstrated that an amblyopia had developed in the treated eyes. Furthermore, the relative magnitude of the amblyopia across spatial frequencies was similar to the relative magnitude of the defocus. Subsequently testing at 1 year of age demonstrated that the deficits persisted for several months after termination of the defocus rearing. This rearing procedure appears to provide a reasonable primate model with which to study anisometropic amblyopia in monkeys.

Age Factors↗

Visual acuity and behavior of monocularly deprived monkeys after retinal lesions.

One eyelid of each of three Macaca nemestrina monkeys was sutured shut at 3 weeks of age. One animal had the central 10 degrees of the open eye retina lesioned at 3 weeks of age (EL1), a second at 9 months of age (LL1), and the third had no lesion (MD1). After a reverse suture at 9 months of age, the deprived eye was tested for grating acuity, visual behavior, and visual field. EL1 tested positively on all behavioral tasks by 1 month and showed good visual ability to negotiate a playroom but never performed better than 20/1,250 on grating acuity. MD1 showed little visual behavior in the playroom but tested at 20/400 acuity. LL1 rapidly recovered all aspects of visual behavior and tested at 20/80 visual acuity. Perimetry shows that LL1 and EL1 respond mainly in the central portion of the deprived eye visual field but not to the periphery or the monocular segment. We conclude that removal of the open eye retina after the critical period allows much visual recovery by the deprived eye but that removal of the open eye retina within the critical period does not prevent many of the effects of monocular deprivation.

Animals↗

Herpesvirus hominis encephalitis and retinitis.

A previously healthy 44-year-old man died three weeks after the simultaneous onset of encephalitis and retinitis. Fundus changes were bilateral and included papillitis, rapidly progressive central retinal vein obstruction, and massive exudative retinal detachment. A 16-fold rise in herpesvirus hominis antibodies occured between the 10th and 20th days of illness. At autopsy, the brain showed changes characteristic of herpetic encephalitis, and cultures of the brain yielded Herpesvirus hominis type I. Intranuclear inclusion bodies typical of those produced by Herpesvirus were found by light microscopy in brain, optic nerves, retina, and choroid. Herpesvirus particles were found by electron microscopy in brain, optic nerve, and retina.

Adult↗