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J Altman

Publications and source records attributed to J Altman.

At least 55 records · Page 3Linked to original sources
PubMed1989

Development of the rat thalamus: VI. The posterior lobule of the thalamic neuroepithelium and the time and site of origin and settling pattern of neurons of the lateral geniculate and lateral posterior nuclei.

Short-survival, sequential, and long-survival thymidine radiograms of rat embryos, fetuses, and young pups were analyzed in order to determine the time of origin, site of origin, migratory route, and settling pattern of neurons of the dorsal lateral geniculate (LGD), ventral lateral geniculate (LGV), and lateral posterior (LP) nuclei of the thalamus. Quantitative examination of long-survival radiograms established that the neurons of the LGD are produced on days E14 and E15. Within the LGD there is an external-to-internal neurogenetic gradient; the majority (77%) of neurons of the external half are generated on day E14, while in the internal half the majority (64%) of neurons originate on day E15. The late-generated LGD neurons are located in the termination field of the uncrossed fibers of the optic tract. Examination of short-survival radiograms indicated that the neurons of the LGD originate in a discrete neuroepithelial eversion situated ventral to the pineal rudiment and dorsal to the putative neuroepithelium of the ventral nuclear complex. In sequential radiograms from rats injected with 3H-thymidine on day E15 and killed on days E16 and E17, the migration of young LGD neurons was followed in a posterolateral direction to the formative lateral geniculate body. By day E17, the day when the optic tract fibers begin to disperse over the lateral surface of the posterior diencephalon, the distribution of early and late-generated neurons of the LGD resembles that seen in young pups. As a whole, the neurons of the LGV are produced earlier than the neurons of the LGD. The bulk of LGV neurons are generated on days E14 and E15 in a caudal-to-rostral intranuclear neurogenetic gradient. Caudal LGV neurons are generated mainly on day E14 (82%), while a substantial proportion of rostral neurons (32%) are generated on day E15. Examination of short-survival and sequential radiograms suggest that the LGV neurons originate in an inverted sublobule situated beneath the putative neuroepithelium of the LGD. At anterior levels the putative inverted sublobule of the LGV merges imperceptibly with the neuroepithelium that produces the neurons of the lateral habenular nucleus. Like the neurons of the LGD and LGV, so also those of the LP are generated on days E14 and E15, but the neurogenetic gradients are different. There is a lateral-to-medial gradient within the LP as a whole. Peak production of neurons is on day E14 laterally (58%) and on day E15 medially (59%).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

Enhancement of natural killer cell activity by Nocardia opaca fractions.

Three molecules derived from Nocardia opaca bacteria, NDCM, NWSMP, and PG, have been shown to express immunomodulating properties. The present study was aimed at assessing the effects of these derivatives on natural killer (NK) activity. Two experimental protocols were adopted, consisting of incubating whole or Percoll fractionated NK cells in vitro with those substances, and the other in which the derivatives were administered in vivo to mice and the activity assessed later. Incubation of spleen cells in vitro with NWSMP or its precursor NDCM promoted NK activity. This effect could be observed after only 2 h of incubation and continued until day 2. Percoll fractions 1-3, which contain most of the NK activity, were enhanced to a similar extent. Band 4, which is usually devoid of such activity, remained unresponsive even after contact with the N. opaca derivatives. PG was practically ineffective upon all the subsets. The results of experiments in vivo correlated with those obtained in vitro in that NWSMP and NDCM, but not PG, promoted NK activity. Bands 1-3 were similarly enhanced, the effect was observed after short treatment times, and could be partially cancelled by the concomitant administration of anti-interferon antibodies (anti-IFN Ab). All these findings suggest that the promoting effects of N. opaca derivatives are mediated through alpha/beta IFN. In contrast to the results observed on spleen NK cells, NK cells from the peritoneum displayed susceptibility mainly to PG, and much less to NWSMP or NDCM. The administration of PG to mice in vivo had a particularly marked promoting effect upon the cytotoxic activity of peritoneal cells. One logical explanation for the difference observed between PG and NWSMP or NDCM may be related to the specific IFN inducing properties of these compounds as well as to the different responsiveness of the NK cells present in the spleen and peritoneal cavity.

Animals↗
PubMed1988

Development of the rat thalamus: I. Mosaic organization of the thalamic neuroepithelium.

Short-survival, sequential, and long-survival thymidine radiograms of rat embryos, fetuses and young pups were analyzed in order to delineate the boundaries of the proliferative thalamic neuroepithelium, describe its early transformations, identify its regional divisions, and, finally, attempt to relate its distinct neuroepithelial components to specific thalamic nuclei that they supply with neurons. On day E13 the thalamic neuroepithelium consists of two divisions, the rostral lobe and the caudal lobe, and interposed between the two is a small transient structure, the reticular protuberance. By day E14 the rostral lobe has become partitioned into the anterior lobule and the reticular lobule, and the caudal lobe into the intermediate lobule and the posterior lobule. By day E15 these four lobules have become further partitioned into sublobules, characterized as regional eversions and inversions (concavities and convexities) of the thalamic neuroepithelium. Several of these sublobules are still recognizable on day E16 but progressively disappear thereafter. In this introductory paper, some evidence is presented in support of the hypothesis that the identified thalamic sublobules represent putative cell lines committed to produce neurons for specific, early-generated thalamic nuclei. Detailed documentation of the evidence on which the identifications are based is provided in subsequent papers of this series which deal with the early development of specific thalamic regions and nuclei. In our attempt to identify these putative cell lines, we sought to meet the following criteria: (1) a good match between the time course of mitotic activity in a neuroepithelial sublobule and the birth days of neurons in the nucleus that it is postulated to supply with neurons, (2) relative proximity between the putative neuroepithelial source and the thalamic target structure, and, where possible, (3) the tracing of migrating cells from the germinal source to its destination. Using these criteria we have made the following tentative identifications. The early derivatives of the anterior thalamic lobules are the sublobules (committed cell lines) of the anterior thalamic nuclei, and of the central lateral and mediodorsal nuclei. The early derivatives of the reticular lobule and reticular protuberance are the sublobules of the reticular nuclear complex. The early derivatives of the intermediate lobule are the sublobules of the ventrolateral and ventrobasal nuclei. Finally, the early derivatives of the posterior lobule are the sublobules of the dorsal geniculate, ventral geniculate, and medial geniculate nuclei.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1988

Development of the rat thalamus: II. Time and site of origin and settling pattern of neurons derived from the anterior lobule of the thalamic neuroepithelium.

Short-survival, sequential, and long-survival thymidine radiograms of rat embryos, fetuses, and young pups were analyzed in order to examine the time of origin, settling pattern, and neuroepithelial site of origin of the anterior thalamic nuclei--the lateral dorsal (lateral anterior), anterodorsal, anteroventral and anteromedial nuclei--and of two rostral midline structures--the anterior paraventricular and paratenial nuclei. The neurons of the lateral dorsal nucleus are generated over a 3-day period between days E14-E16 and their settling pattern displays a combined lateral-to-medial and dorsal-to-ventral neurogenetic gradient. The bulk of the neurons of the anteroventral nucleus are generated over a 3-day period between days E15-E17 and settle with an oblique lateral-to-medial and ventral-to-dorsal neurogenetic gradient. The bulk of the neurons of the anteromedial nucleus are generated over a 2-day period between days E16-E17 and show the same settling pattern as the anteroventral nucleus. The neurons of the anterodorsal nucleus are generated over a 3-day period between days E15-E17 and show a lateral-to-medial neurogenetic gradient. The bulk of the neurons of the central part and lateral part of the paraventricular nucleus are generated over a 2-day period (E16-E17 and E17-E18, respectively) and each part displays a ventral-to-dorsal neurogenetic gradient. Finally, the bulk of the neurons of the paratenial nucleus are generated over a 4-day period between days E15-E18 and settle with a lateral-to-medial neurogenetic gradient. Observations are presented that the anterior thalamic nuclei, constituting the distinct "limbic thalamus," derive from a discrete neuroepithelial source. This is the crescent-shaped germinal matrix lining the diencephalic (medial) wall of the hitherto unrecognized anterior transitional promontory, which we call the anterior thalamic neuroepithelial lobule. On day E16 three migratory streams leave the anterior neuroepithelial lobule and, on the basis of their labeling pattern in relation to the neurogenetic gradients of the anterior thalamic nuclei, they are identified, from dorsal to ventral, as the putative migratory streams of the anterodorsal, anteroventral, and lateral dorsal nuclei. On day E17 the putative migratory stream of the anteromedial nucleus appears to leave the same neuroepithelial region that on the previous days was the source of the anteroventral nucleus. Dorsally, two neuroepithelial patches persist after day E17 and these are identified as the putative cell lines of the anterior paraventricular and paratenial nuclei.

Animals↗
PubMed1988

Development of the rat thalamus: III. Time and site of origin and settling pattern of neurons of the reticular nucleus.

Short-survival, sequential, and long-survival thymidine radiograms of rat embryos, fetuses, and young pups were analyzed in order to examine the time of origin, settling pattern, migratory route, and site of origin of neurons of the reticular nuclear complex of the thalamus. On the basis of its chrono-architectonics, the reticular nucleus was divided into a central, medial, and lateral subnucleus. The central subnucleus is the earliest produced component of the entire thalamus with over 50% of its neurons being generated on day E13 and another 40% on day E14. Peak production of neurons of the lateral and medial subnuclei is on day E14. There is a lateral (earlier) to medial (later) neurogenetic gradient between these two components of the reticular complex: only about 12% of the lateral subnucleus neurons, but close to 30% of the medial subnucleus neurons, are generated on day E15. Because the lateral and medial subnuclei display the typical outside-in gradient found in the thalamus, they are considered to constitute a single cytogenetic sector; the early generated central subnucleus, which violates this order, is considered to constitute a separate cytogenetic sector. Observations are presented that neurons of the central reticular subnucleus originate in a unique neuroepithelial region, the reticular protuberance. The migration of heavily labeled cells was traced from this region in rats labeled with 3H-thymidine on day E13 and killed on the subsequent days. The neurons of the lateral and medial reticular subnuclei originate in the reticular lobule of the thalamic neuroepithelium. The migration of heavily labeled, spindle-shaped cells was traced from this region in rats labeled with 3H-thymidine on days E14 and E15 and killed at daily intervals thereafter. The neurogenetic gradient of the reticular thalamic complex seen in postnatal rats is established before birth.

Animals↗
PubMed1987

Development of the preoptic area: time and site of origin, migratory routes, and settling patterns of its neurons.

Neurogenesis and morphogenesis in the rat preoptic area were examined with [3H]thymidine autoradiography. For neurogenesis, the experimental animals were the offspring of pregnant females given an injection of [3H]thymidine on two consecutive gestational days. Nine groups were exposed to [3H]thymidine on embryonic days E13-E14, E14-E15, E21-E22, respectively. On postnatal day P5, the percentage of labeled cells and the proportion of cells originating during 24-hr periods were quantified at four anteroposterior levels in the preoptic area. Throughout most of the preoptic area there is a lateral to medial neurogenetic gradient. Neurons originate between E12-E15 in the lateral preoptic area, between E13-E16 in the medial preoptic area, between E14-E17 in the medial preoptic nucleus, and between E15-E18 in the periventricular nucleus. These structures also have intrinsic dorsal to ventral neurogenetic gradients. There are two atypical structures: (1) the sexually dimorphic nucleus originates exceptionally late (E15-E19) and is located more lateral to the ventricle than older neurons; (2) in the median preoptic nucleus, where older neurons (E13-E14) are located closer to the third ventricle than younger neurons (E14-E17). For an autoradiographic study of morphogenesis, pregnant females were given a single injection of [3H]thymidine during gestation, and their embryos were removed either two hrs later (short survival) or in successive 24-hr periods (sequential survival). Short-survival autoradiography was used to locate the putative neuroepithelial sources of preoptic nuclei, and sequential survival autoradiography was used to trace the migratory waves of young neurons and their final settling locations. The preoptic neuroepithelium is located anterior to and in the front wall of the optic recess. The neuroepithelium lining the third ventricle is postulated to contain a mosaic of spatiotemporally defined neuroepithelial zones, each containing precursor cells for a specific structure. The neuroepithelial zones and the migratory waves originating from them are illustrated. Throughout most of the preoptic area, neurons migrate predominantly laterally. The older neurons in the lateral preoptic area migrate earlier and settle adjacent to the telencephalon. Younger neurons migrate in successively later waves and accumulate medially. The sexually dimorphic neurons are exceptional since they migrate past older cells to settle in the core of the medial preoptic nucleus.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1987

Development of the precerebellar nuclei in the rat: I. The precerebellar neuroepithelium of the rhombencephalon.

Short-survival thymidine radiograms from rat embryos aged 13-19 days were analyzed to delineate the precerebellar neuroepithelium of the rhombencephalon. The original definition of the term "rhombencephalon" was modified to refer only to the unique dorsal portion (surface plate) of the medulla and pons where the neural groove fails to fuse and, instead, the medullary velum covers the rhomboid lumen of the fourth ventricle. Initially, the neuroepithelial tissue of the rhombencephalon consists of a pair of rostral and caudal bridgeheads: the former the primary neuroepithelium of the cerebellum and the latter the primary neuroepithelium of the octavo-precerebellar system. The spatial relationship between the cerebellar and precerebellar neuroepithelia soon changes as a result of ongoing morphogenetic events, such that the cerebellar primordium assumes a dorsal position and the precerebellar primordium a ventral position, and the distance between the two decreases. Concurrently the tela choroidea invaginates into the fourth ventricle and a secondary precerebellar neuroepithelium develops. The rostral portion of the secondary precerebellar neuroepithelium grows forward along the choroid plexus and forms the medial recess of the anterior fourth ventricle, while its caudal portion grows in the opposite direction beneath the medullary velum and forms the rostral wall of the posterior fourth ventricle. Evidence will be presented in the succeeding papers that the primary precerebellar neuroepithelium first generates the neurons of the inferior olive that migrate by a circumferential intramural (parenchymal) route to their destination. Next, the neurons of the lateral reticular and external cuneate nuclei are generated. These migrate by a posterior extramural (superficial) route and settle contralaterally. Subsequently, the primary precerebellar neuroepithelium produces the neurons of the nucleus reticularis tegmenti pontis and these form the anterior extramural migratory stream and settle ipsilaterally. Finally, the secondary precerebellar neuroepithelium produces the latest generated neurons of the basal pontine gray that follow the anterior extramural stream and settle ipsilaterally.

Animals↗
PubMed1987

Development of the precerebellar nuclei in the rat: II. The intramural olivary migratory stream and the neurogenetic organization of the inferior olive.

Sequential thymidine radiograms from rats labeled on days E13 and E14, and killed at daily intervals thereafter, were analyzed to trace the migratory route and settling pattern of neurons of the inferior olive. Long-survival thymidine radiograms from perinatal rats injected on day E14 were used to subdivide the inferior olivary complex on the basis of neurogentic criteria. The inferior olivary neurons originate on days E13 and E14 in the primary precerebellar neuroepithelium. The olivary neurons labeled on day E14 (the late generated components) translocate into the inferior olivary premigratory zone on day E15. On day E16 these cells join the olivary migratory stream, which follows an intramural circumferential path between the gray and white matters of the medulla. By day E17 the olivary migratory stream is reduced to a small band near the corpus of the inferior olive, which has been settled by this time by neurons generated on day E13. As a result, the unlabeled cells are situated on day E17 dorsomedially and the labeled cells ventrolaterally. The regional segregation of neurons forming subdivisions of the inferior olive begins on day E18, and by day E19 the major subdivisions are all recognizable. In thymidine radiograms from perinatal rats injected on day E14, four neurogenetic components can be distinguished in the inferior olive, those composed: (1) of unlabeled cells (generated on day E13), (2) of predominantly unlabeled cells, (3) of predominantly labeled cells (generated on day E14), and (4) of labeled cells. By combining these neurogenetic differences with the morphological features of the inferior olivary complex, we propose a modification of the currently accepted classification. The four major divisions of the inferior olive are the successively produced posterodorsal olive, anterolateral (principal) olive, posteroventral olive, and anteroventral olive. The location and configuration of these divisions are illustrated in relation to the traditional classification both in the coronal and the sagittal plane.

Animals↗
PubMed1987

Development of the precerebellar nuclei in the rat: III. The posterior precerebellar extramural migratory stream and the lateral reticular and external cuneate nuclei.

Sequential thymidine radiograms from rats injected on day E15 and killed thereafter at daily intervals up to day E22 were analyzed to trace the migratory routes and settling patterns of neurons of the lateral reticular nucleus and the external cuneate nucleus. The neurons of the lateral reticular and external cuneate nuclei originate in the primary precerebellar neuroepithelium at the same site as the inferior olivary neurons but follow a different migratory route. The labeled young neurons that are produced on day E15 (the last one-third of the total) join the posterior precerebellar extramural migratory stream. The cells move circumferentially over the wall of the medulla in a ventral direction and by day E17 reach the midline and cross it beneath the inferior olive. The crossing cells apparently continue to migrate circumferentially on the opposite side. One complement of these cells begins to form a ventrolateral extramural condensation on day E19. By day E20 some cells begin to penetrate the parenchyma and settle as neurons of the lateral reticular nucleus. The settling of the lateral reticular neurons continues on the following day, and by day E22 all the cells destined for the lateral reticular nucleus have penetrated the parenchyma. A dorsomedial-to-ventrolateral neurogenetic gradient is indicated for the settling lateral reticular neurons. Another complement of migrating cells continues dorsally and forms a condensation on day E19 that we interpret as the external cuneate component of the crossed stream. These cells begin to penetrate the parenchyma on day E20, and by days E21 and E22 two components of the external cuneate nucleus are identifiable-the dorsal and ventral external cuneate nuclei. The neurons of the lateral reticular and external cuneate nuclei differ from neurons of all the other precerebellar nuclei in that their cerebellar projection is predominantly ipsilateral. We speculate that the axons of all precerebellar neurons are genetically specified to cross the midline ventrally to provide a contralateral efferent projection, but this is modified in the case of the ipsilaterally projecting lateral reticular and external cuneate neurons by the cell bodies following their neurites to the opposite side.

Animals↗
PubMed1987

Development of the precerebellar nuclei in the rat: IV. The anterior precerebellar extramural migratory stream and the nucleus reticularis tegmenti pontis and the basal pontine gray.

Sequential thymidine radiograms from rats injected on days E16, E17, E18, and E19 and killed 2 hours after injection and at daily intervals up to day E22 were used to establish the site of origin, migratory route, and settling patterns of neurons of the nucleus reticularis tegmenti pontis and basal pontine gray. The nucleus reticularis tegmenti pontis neurons, which are produced predominantly on days E15 and E16, derive from the primary precerebellar neuroepithelium. These cells, unlike those of the lateral reticular and external cuneate nuclei, take an anteroventral subpial route, forming the anterior precerebellar extramural migratory stream. This migratory stream reaches the anterior pole of the pons by day E18. In rats injected on day E16 and killed on day E18 some of the cells that reach the pons are unlabeled, indicating that they represent the early component of neurons generated on day E15. The cells labeled on day E16 begin to settle in the pons on day E19, 3 days after their production. These cells, migrating in an orderly temporal sequence, form a posterodorsal-to-anteroventral gradient in the nucleus reticularis tegmenti pontis. Unlike the neurons of all the other precerebellar nuclei, the basal pontine gray neurons derive from the secondary precerebellar neuroepithelium. The secondary precerebellar neuroepithelium forms on day E16 as an outgrowth of the primary precerebellar neuroepithelium, and it remains mitotically active through day E19, spanning the entire period of basal pontine gray neurogenesis. The secondary precerebellar neuroepithelium is surrounded by a horizontal layer of postmitotic cells, representing the head-waters of the anterior precerebellar extramural migratory stream. In rats injected on day E18 and killed on day E19 the cells are labeled in the proximal half of the stream around the medulla but those closer to the pons are unlabeled, indicating an orderly sequence of migration. In rats injected on day E18 and killed on day E20 the labeled cells reach the pole of the pons. In the basal pontine gray the sequentially generated neurons settle in a precise order. The neurons generated on day E16 form a small core posteriorly and the neurons generated on days E17, E18, and E19 form regular concentric rings around the core in an inside-out sequence.

Animals↗
PubMed1987

A comparison of oral midazolam, nitrazepam and placebo in young and elderly subjects.

Twelve young and twelve elderly subjects received a single dose orally of midazolam 15 mg, nitrazepam 5 mg and placebo in a double-blind, crossover comparison. Midazolam acted rapidly, producing a deep sleep at 1 h in fifteen subjects compared to two after Nitrazepam and none after placebo. No comparison of psychomotor tests was possible at this time, but such tests showed that there was no detectable subjective or objective psychomotor impairment at 4 h postdose with either drug. However, the EEG scores strongly suggested that volunteers were more sleepy at 8 h after nitrazepam in comparison to placebo or midazolam. Both groups appeared to handle the drug in a similar manner, there being no significant differences between the groups in the plasma concentration time curves of nitrazepam, or midazolam. The elderly had higher concentrations of alpha-hydroxymidazolam. This accounted for a small proportion of the total plasma benzodiazepine concentration, and the mean area under the curve for midazolam and metabolite was not significantly different in the old from that in the young.

Adult↗
PubMed1987

Morphological and behavioral markers of environmentally induced retardation of brain development: an animal model.

In most neurotoxicological studies morphological assessment focuses on pathological effects, like degenerative changes in neuronal perikarya, axonopathy, demyelination, and glial and endothelial cell reactions. Similarly, the assessment of physiological and behavioral effects center on evident neurological symptoms, like EEG and EMG abnormalities, resting and intention tremor, abnormal gait, and abnormal reflexes. This paper reviews briefly another central nervous system target of harmful environmental agents, which results in behavioral abnormalities without any qualitatively evident neuropathology. This is called microneuronal hypoplasia, a retardation of brain development characterized by a quantitative reduction in the normal population of late-generated, short-axoned neurons in specific brain regions. Correlated descriptive and experimental neurogenetic studies in the rat have established that all the cerebellar granule cells and a very high proportion of hippocampal granule cells are produced postnatally, and that focal, low-dose X-irradiation either of the cerebellum or of the hippocampus after birth selectively interferes with the acquisition of the full complement of granule cells (microneuronal hypoplasia). Subsequent behavioral investigations showed that cerebellar microneuronal hypoplasia results in profound hyperactivity without motor abnormalities, while hippocampal microneuronal hypoplasia results in hyperactivity, as well as attentional and learning deficits. There is much indirect clinical evidence that various harmful environmental agents affecting the pregnant mother and/or the infant lead to such childhood disorders as hyperactivity and attentional and learning disorders. As the developing human brain is more mature at birth than the rat brain, the risk for microneuronal hypoplasia and consequent behavioral disorders may be highest at late stages of fetal development, in prematurely born and small-for-weight infants, and during the early stages of infant development. Recent technological advances in brain imaging techniques make it possible to test this hypothesis and to assess the possible relationship between the degree of retarded brain development and ensuing behavioral disorders.

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