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Biomedical subjects

J Altman

Publications and source records attributed to J Altman.

At least 127 records · Page 7Linked to original sources

Development of the diencephalon in the rat. II. Correlation of the embryonic development of the hypothalamus with the time of origin of its neurons.

The development of the nuclei of the hypothalamus was examined in normal and X-irradiated embryos from day 13 (E13) to the day before birth (E22). The diencephalic neuroepithelium was subdivided into three lobes (dorsal, medial, and ventral) and two lobules (superior and inferior). The hypothalamus is derived from the ventral lobe and the inferior lobule. The ventral neuroepithelial lobe generates the neurons of most of the early arising hypothalamic structures, including those of the lateral tier nuclei associated with the medial forebrain bundle, and the heterogeneous intermediate tier nuclei. A specialized neuroepithelial region lining the diamond shaped ventricle produces the early neurohypophysial magnocellular neurons; the neurons of the paraventricular nucleus remain at this site, whereas the neurons of the supraoptic nucleus could be traced migrating laterally. The neurons of the late arising hypophysiotropic area of the posterior hypothalamus are derived from components of the inferior neuroepithelial lobule: the dorsomedial and ventromedial nuclei apparently from a shared matrix in the main portion of the inferior lobule; the tuberomammillary-arcuate complex from its posteroventral recess. The triple-decked and sequentially produced components of the mammillary system may arise from separate neuroepithelial sites. The autoradiographic results of the previous study (Altman and Bayer, '78a) showed that the structural and functional heterogeneity of the mature hypothalamus is paralleled by cytogenetic heterochronicity; the present embryonic observations indicate that many of the distinguishable components of the hypothalamus arise from a mosaic of heterogeneous neuroepithelial sites.

Animals↗

Development of the diencephalon in the rat. III. Ontogeny of the specialized ventricular linings of the hypothalamic third ventricle.

The development of the specialized linings of the hypothalamic third ventricle was examined autoradiographically in mature rats that were labelled with 3H-thymidine during the developmental period, and in a closely spaced series of embryonic and infant rats. We distinguished in mature rats, apart from the typical ependymal wall, three specialized linings: the convoluted ependyma, the laminated epithelium, and the tanycytic epithelium. The ventricular wall of most of the anterior hypothalamus, and of the dorsal portion of the posterior hypothalamus, is composed of ciliated ependymal cells and most of them are generated several days before birth, soon after the cessation of neurogenesis in the adjacent hypothalamic nuclei. The cells of the rostral convoluted ependyma adjacent to the paraventricular nucleus are produced at about the same time as the neighboring cells of the smooth ependyma. Its cells come from the same germinal region that we have assumed to generate the neurons of the magnocellular neurohypophysial secretory system. The structural differentiation of the convoluted ependyma starts after birth and is completed by the beginning of the second week. Many of the ependymal cells of the laminated epithelium are produced postnatally, and the production of the specialized cells that form a parallel subependymal row extends into the third week. These cells appear to arise from the same matrix that generates earlier the neurons of the dorsomedial and ventromedial hypothalamic nuclei; their structural differentiation begins during the second week. Also the cells of the tanycytic epithelium are produced mostly postnatally, predominantly during the first week. They appear to arise from the same matrix that generated earlier the neurons of the hypophysiotropic tuberomammillary and arcuate nuclei. It is postulated that these three specialized ventricular linings are specifically related to the three cpmponents of the endocrine hypothalamus with which they have shared neuroepithelial sites of origin.

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Speckled lentiginous nevus.

Speckled lentiginous nevus is, we feel, a distinctive nevocytic disorder and a clinical variety of nevus-cell nevus. The speckled areas show varying histological patterns that range from nevus incipiens to junctional and compound nevi. The background shows histological features of lentigo simplex. It is our contention that speckled lentiginous nevus should be separated from nevus spilus and nevus spilus tardus (Becker's), which we consider to be variants of epidermal nevus.

Adolescent↗

Time of origin and distribution of a new cell type in the rat cerebellar cortex.

A new cell type was identified in the granular layer of the rat cerebellum. It has a lightly staining nucleus with a nucleolus, it is spherical in shape and is larger than granule cells and smaller than Golgi cells. These pale cells are preferentially concentrated in the nodulus, the ventral uvula, the lingula, the flocculus, and parts of the paraflocculus. According to autoradiographic (3H-thymidine) evidence, over 60% of these pale cells are formed on embryonic days 19 and 20, and their production comes to an end soon after birth, prior to the differentiation of granule cells. The possible relation of pale cells to vestibular afferents of the cerebellar cortex is discussed.

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The effect of ethanol chronically administered to preweanling rats on cerebellar development: a morphological study.

The effects of ethanol on body, brain and cerebellar growth of the postnatal rat have been studied. Vapor inhalation, the procedure used to administer ethanol directly to preweanling (3-20-day-old) rats, produced maximal blood ethanol levels that averaged 239 mg/100 ml. Weight determinations indicated that brain but not body growth was significantly stunted by exposure to ethanol. Moreover, cerebellar growth, which occurred largely but not wholly during the period of ethanol treatment, was inhibited twice as much as the rest of the brain. Arrested brain and cerebellar growth appeared shortly after ethanol treatment was begun and persisted into adulthood following a postweaning rehabilitation period. Ethanol treatment diminished the growth of both the anterior and posterior lobes and of all layers of the cerebellar vermis. However, the effect of ethanol was larger in the anterior lobe than the posterior lobe, and the medullary layer was more retarded than the others. Some compensatory growth occurred in the molecular and granular layers of the experimental rats during a postweaning rehabilitation period. The effects of ethanol on 2 major neuronal populations of the cerebellar cortex -- the large, prenatally-formed Purkinje cells and the small, postnatally-formed granule cells -- were assessed via light microscopy. After 2 days of ethanol treatment the number of Purkinje cells in all 10 vermal lobules was reduced; neither additional exposure to ethanol nor a postweaning rehabilitation period subsequently altered cell number. The possibility that the regional magnitude of the Purkinje cell loss was related to the chronology of lobular development was discussed; Purkinje cells in the latest maturing lobules being least affected. The morphological development of surviving Purkinje cells proceeded normally. An autoradiographic study indicated the pattern of granule cell neurogenesis in cerebella of ethanol-treated rats and of control rats did not differ, although the experimental animals had consistently fewer cells in all stages of development. The ultimate loss of 20-25% of their granule cells was accounted for by an early diminution of the stem cell population of the external germinal layer by about 10%. The results suggest the initial targets of ethanol were the immature Purkinje cells, which were reduced in number before the onset of granule cell formation. A complex age-dependent interaction between blood ethanol levels and vulnerable periods in Purkinje cell development was suggested. Mechanisms for the subsequent correlative reduction in the granule cell population were also discussed.

Age Factors↗

Postnatal development of the cerebellar cortex in the rat. V. Spatial organization of purkinje cell perikarya.

The development of the spatial organization of Purkinje cell perikarya was examined in the rat cerebellum from birth to adulthood. Dispersion of the perikarya following birth is made possible by the rapid expansion of the cortical surface. Their subsequent regular monocellular alignment is ensured by mechanical factors, the pressure exerted from below by the expanding granular layer and the barrier formed above by the pile of parallel fibers which prevent the penetration of the bulky perikarya into the molecular layer. The perikarya remain in this position even after the slender stem dendrite pierces the molecular layer along the descending axons of basket cells. The increase in interperikaryal distance between Purkinje cells is rapid up to day 12, then declines. This is temporally associated with the growth of the basket cell plexus and glial envelope around the perikaryon. The increase in perikaryal size continues up to day 30. This may be temporally associated with the growth of the Purkinje cell dendritic arbor as reflected by the expansion of the molecular layer up to day 30. The spatial arrangement of Purkinje cells within the monocellular sheet was graphically displayed with computer aid. In the adult cerebellum a hexagonal arrangement could be recognized in a proportion of "near-neighborhoods," consisting of about six Purkinje cells and their neighbors. When the neighborhoods were extended with fixed orientation with respect to the axis of the folium, the hexagonal arrangement disappeared. When orientation was ignored, the superimposed near-neighborhoods could be rotated to produce a hexagonal pattern. In the infant cerebellum the hexagonal arrangement could not be demonstrated before the alignment of Purkinje cells in a monolayer. Thereafter there appeared to be an increase with age in the proportion of hexagonally arranged near-neighborhoods. It was concluded that in the monocellular ganglionic layer Purkinje cells are not aligned in regular rows with respect to the geometrically arranged elements of the supraganglionic layer. The formation of an imprecise hexagonal pattern, like the alignment of Purkinje cells in a monolayer, was attributed to mechanical factors.

Age Factors↗

Evidence for a visceral smooth muscle abnormality in Okamoto spontaneous hypertension.

1. In order to discover whether the changes in reactivity are related to the primary cause of hypertension in spontaneously hypertensive rats (SHR) or are just an adaptation induced by the high arterial blood pressure we tested the contractile response of a visceral smooth muscle from such rats. 2. Longitudinal strips of the fundus from 20 week old male and female SHR and Wistar normotensive (NW) rats were used. Dose-response curves to Ba2+ in SHR strips were displaced to the right as compared to NW rats. Maximal responses were identical. Male SHR fundus strips contracted much more with Sr2+ (SHR: 42+/-3% of maximum response to Ba2+, n=10; NW: 19+/-4%, n=10, P less than 0.01) than NW strips. There was no difference in the response to both BaCl2 and SrCl2 between female SHR and NW fundus strips, and MnCl2 and LaCl3 were relaxant in all cases. 3. Dose-response curves to Ca2+ of depolarized SHR and NW fundus strips were obtained and the effect of diazoxide on Ca2+ contractions was observed. The contractile action of Ca2+ in depolarized preparations was enhanced in both male and female SHR strips. The effect of diazoxide was more marked in SHR strips than in NW fundus strips. 4. SHR fundus smooth muscle shows the same modification of reactivity to Ba2+, Sr2+, Ca2+ and diazoxide that was previously described in arterial smooth muscle. This indicates that the cellular modification responsible for the increase of vascular tonus in SHR is not an adaptive reaction to high blood pressure. The differences between female SHR and male SHR responses are not unexpected, considering the natural evolution of hypertension in Okamoto rats which is milder in the female.

Animals↗

Experimental reorganization of the cerebellar cortes. V. Effects of early x-irradiation schedules that allow or prevent the acquisition of basket cells.

In neonate and infant rats the area of cerebellum was irradiated with different schedules of single or multiple doses of low-level X-ray. One set of schedules allowed the early recovery of the external germinal layer and the differentiation of all the postnatally-forming cell types while the other selectively prevented the acquisition of basket cells. The first schedule did not interfere with the development of normally oriented and arborizing Purkinje cells. The second schedule led to the growth of twisted and entwined stem dendrites even when, in association, with the recovered granule cells, parallel fibers were present in the molecular layer together with Purkinje cell spiny branchlets. Evidence was presented that the alignment of Purkinje cell perikarya in a monolayer does not guarantee the normal growth of Purkinje cell stem dendrites which may be dependent on the presence of basket cells. The problem was discussed whether cell differentiation in the cerebellar cortex is governed by a chronological or sequential principle.

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Experimental reorganization of the cerebellar cortes. VI. Effects of x-irradiation schedules that allow or prevent cell acquisition after basket cells are formed.

In Long-Evans rats the area of the cerebellum was X-irradiated with two schedules beginning on day 8 by which time the bulk of basket cells were formed. The shorter schedule of four successive daily doses of 200 r between 8-11 days was designed to allow some cell recovery, the longer schedule between 8-15 days was expected to prevent it. Neither of the schedules interfered with the differentiation of basket cells. Purkinje cells remained aligned in a monocellular layer and formed singularly long, upright stem dendrites which were surrounded by the descending collaterals of basket cell axons. This supported the hypothesis that the directed growth of Purkinje cell stem dendrite is promoted by morphogenic interaction with basket cells. The upright stem dendrites had few or no smooth branches where cell recovery was prevented or had few such branches where recovery occurred. It was postulated that the out-growth of smooth branches is dependent on interaction with stellate cells which form after the acquisition of basket cells. The absence or scarcity of smooth branches did not prevent the formation of spiny branchlets which grew downward to establish synaptic contacts with the spared parallel fibers of granule cells formed before the start of irradiation. In the group with some granule cell recovery, spiny branchlets grew to a limited extent upward into the pile of parallel fibers formed after the irradiation.

Animals↗

Experimental reorganization of the cerebellar cortex. VII. Effects of late x-irradiation schedules that interfere with cell acquisition after stellate cells are formed.

In Long-Evans rats the area of the cerebellum was irradiated with multiple doses of low-level X-ray beginning on day 12 after the bulk of stellate cells were acquired. The treatment spared basket, stellate and early-forming granule cells but led to a substantial reduction in the total granule cell population and a correlated miniaturization of the cerebellar cortex. Nevertheless most Purkinje cells had normally shaped planar dendritic arbors, with an upward directed stem dendrite, several smooth branches and a multitude of spiny branchlets. The frequency piling up of spiny branchlets near the surface was attributed to the truncation of the bed of parallel fibers by this radiation schedule. In this last paper of the series the accumulated results are summarized and evaluated. The hypothesis is offered that while the growth of the Purkinje cell perikaryon is an autonomous process, the oriented perpendicular growth of a single stem dendrite depends on the presence of basket cell axons, the outgrowth of smooth branches on the presence of stellate cell axons, and the proliferation of spiny branchlets on interaction with parallel fibers. The parallel fibers are responsible for the orthogonal, planar growth of the dendritic arbor and a hypothesis is offered about the mechanisms involved.

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Lack of hypotensive effect on central injection of angiotensin inhibitors in spontaneously hypertensive (SH) and normotensive rats.

1. Injections of antagonists of angiotensin II into the cerebral ventricles of normotensive and spontaneously hypertensive rats were performed in order to assess the role of the isorenin-angiotensin system in the brain. 2. No hypotensive effect was obtained in either normotensive or hypertensive rats, suggesting that intracranial isoangiotensin has little role in the pathogenesis of spontaneous hypertension in the rat.

Angiotensin II↗

[Early renal hemodynamic modifications following the ablation of the controlateral kidney].

Instantaneous measurements of renal blood flow (RBF) and glomerular filtration rate (GFR) have been performed in anesthetized dogs to determine if removal of one kidney induces early functional adaptation in the remaining kidney. Increases in RBF (10%) and GFR (20%) were observed within the first minutes after exclusion of controlateral kidney; these are the earliest events described until now. These observations favour the concept that a functional adjustement may contribute to development of compensatory renal hypertrophy.

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[Effect of furosemide, potassium canrenoate and D-L-propranolol on blood pressure in spontaneously hypertensive rat].

Spontaneously hypertensive rats (japanese strain) have been treated with furosemide, potassium canrenoate or d-l-propranolol. Present results indicate that: 1)furosemide admiinistration, from the 3rd to the 15th week of life, does not prevent the development of hypertension but the blood pressure rises more slowly in treated rats. In the established phase of hypertension furosemide administration produces a decrease in blood pressure; the blood pressure increases rapidly after cessation of the treatment. 2) potassium canrenoate, injected from the 3rd to the 14th week of life, does not prevent the rise in blood pressure.3) d-l-propranolol, administered from the 5th to the 34th week of life, is without effect on the development of hypertension, though it significantly decreases heart rate.

Animals↗