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Biomedical subjects

E J Nathaniel

Publications and source records attributed to E J Nathaniel.

At least 19 recordsLinked to original sources
PubMed1999

Effect of exogenous thyroxine on the development of the Purkinje cell in fetal alcohol effects in the rat.

The amelioration of fetal alcohol effects on the postnatal development of the Purkinje cell by exogenous L-thyroxine was investigated in the neonatal rat. Time-pregnant rats were divided into three groups. Group A (n = 6) received 35% liquid ethanol diet; Group B (n = 6) was fed a liquid diet in which maltose dextrins replaced alcohol isocalorically, constituting the pair-fed group; Group C (n = 6) received the 35% liquid ethanol diet and, in addition, received exogenous thyroxine (5 microg/kg/day) subcutaneously. After the pups were born, the mothers were removed and the pups of each were surrogate fostered by dams who were fed normal rat chow and water ad libitum. An average of six pups, one from each litter, were killed at days 7, 14, 21, and 28 for each of the above three groups. Light and electron microscopic observations of lobule II/III revealed a delayed alignment of Purkinje cells (Pc) in alcohol-exposed pups compared to pair-fed pups. The Pc of the pair-fed group showed a single-layer arrangement at 7 days which was seen only at day 14 in the alcohol group. However, in the alcohol + T(4)-exposed pups a single-layer arrangement was quite often seen at 7 days. Morphological observations showed impaired evidence of protein synthesis at all time sequences in the pups of Group A compared to Group B. A most interesting finding was the morphological evidence of greater protein synthesis in the Pc of the alcohol + T(4) group at all times as indicated by a hypertrophied nucleus, abundant ribosomal collection, and numerous Nissl bodies.

Age Factors↗
PubMed1994

Fetal alcohol effects on the postnatal development of the rat myocardium: an ultrastructural and morphometric analysis.

Heart disease is an entity frequently seen in the fetal alcohol syndrome. This paper describes the effect of in utero ethanol exposure on the postnatal ultrastructural development of rat cardiac muscle. To determine this time-pregnant Sprague-Dawley rats were fed either a nutritionally balanced protein- and vitamin-enriched liquid ethanol diet (with 36% of the calories derived from ethanol) or a liquid diet with maltose-dextrins isocalorically substituted for ethanol. The latter group was designated the pairfed control group. At birth, pups of both the groups were surrogate-fostered by normal dams. Body weights and crown-rump lengths were significantly less in the rat pups exposed to ethanol in utero at 21 days postnatal. Ultrastructural analysis of the cardiac muscle was performed at 7, 14, and 21 days postnatal in ethanol and pairfed groups. Several morphological features of myocyte damage were observed in ethanol-exposed pups, predominantly at 7 days postnatal, with nearly total absence of myocyte damage by 21 days postnatal. The most outstanding changes were observed in the myofibrils, which showed dysplastic changes at 7 days postnatal, a delay in M-band structural development at 14 days postnatal, and a significantly smaller myofibril volume density per tissue volume at 21 days postnatal in the ethanol rat pups compared to the pairfed controls.

Animals↗
PubMed1992

A morphological and morphometric analysis of the optic nerve in the hypothyroid rat.

This investigation was designed to morphologically evaluate the effects of hypothyroidism on the development of myelin and axons in the rat optic nerve. Four pups from each group of normal and propylthiouracil-induced hypothyroid rats were sacrificed at 14, 21, 28, and 35 postnatal days. Optic nerves were studied by both light and electron microscopes. The hypothyroid animals had significantly reduced body and brain weights compared to those of their age-matched controls. In the hypothyroid animals, the cross-sectional area of the optic nerve, the fiber density, and fiber occupancy were significantly diminished compared to those of the controls. The mean individual fiber size was unaffected. However, the relationship between the total axonal area to myelin thickness was similar in the control and experimental groups, implying that the feedback mechanism between myelinating cells and axons was not affected by hypothyroidism. Thus, this study indicates that the principal insult of neonatal hypothyroidism results in a delay in myelin acquisition of myelinated fibers, resulting in diminished cross-sectional area of the optic nerve, fiber density, and fiber occupancy.

Aging↗
PubMed1992

Comparisons of capillary maturation in control and hypothyroid rat spinal cord: an ultrastructural study.

Quantitative and qualitative features of capillary maturation were examined in the ventral horn of the lumbar spinal cord of control and neonatally induced hypothyroid rats from birth to 6 weeks, using light (LM) and electron microscopy (EM). Quantification of the capillary densities by LM in the control animals and their hypothyroid litter mates have shown three- and twofold increases, respectively, from birth to Postnatal (Pn) Day 21. The following features were observed in the control animals at the EM level: (a) The newborn animals showed varying degrees of capillary maturation; (b) The majority of capillaries possessed mature characteristics by Pn Day 21; (c) By Pn Day 42, mature characteristics were found in nearly all capillary profiles. The hypothyroid animals demonstrated: (1) reactive perivascular cells and astrocytes; (2) delayed appearance of glycogen in the early Pn period and its persistence in extensive amounts during the latter part (3-6 weeks) of development; (3) cytoplasmic extensions of endothelial cells and perivascular cells, and (4) the presence of mitotic endothelial cells and perivascular cells even during the latter period of development. The observations suggest that the peak period of vasculogenesis in the lumbar spinal cord of the normal rat occurs during the second and third Pn weeks. The results from the hypothyroid rats point toward a delay in development and maturation of capillaries resulting in a hypoplastic vascular bed of the ventral horn. The reactive cells and the accumulation of glycogen particles could be morphological expressions of biochemical changes in hypothyroidism during the critical period of CNS development.

Aging↗
PubMed1988

Effect of thyroxine replacement therapy on the growth patterns of body, brain, and cerebellum in the neonatal hypothyroid rat.

The reversibility of the effects of propylthiouracil induced neonatal hypothyroidism by daily subcutaneous injections of L-thyroxine (T4) was investigated in the rat. Four groups of rat pups were used in this experiment: Group I (control) received equivalent amounts of saline subcutaneously; Group II (hypothyroid) received propylthiouracil injections daily; Group III (T4-14) are hypothyroid rats who received daily T4 replacement therapy (2.5 micrograms/day) subcutaneously starting on Day 14; Group IV (T4-21) are also hypothyroid rats whose T4 replacement therapy (2.5 micrograms/day) was started on Day 21. The four parameters studied were body length, body weight, brain weight, and cerebellar weight in these four groups of animals at 4, 7, 10, 14, 21, 28, 35, and 42 postnatal days. A minimum of eight animals were studied for each time sequence. The present study clearly indicated the beneficial effect of T4 therapy on the length and body weight of the hypothyroid animals, whether therapy was started at Postnatal Day 14 or 21. In addition, a more important finding of this study was the significant increase in brain and cerebellar weights of T4-treated animals compared to the hypothyroid animals, this beneficial effect being more striking in the T4-14 group when compared to that in the T4-14 animals.

Animals↗
PubMed1987

Altered Purkinje cell maturation in rats exposed prenatally to ethanol. I. Cytology.

Sprague-Dawley pregnant rats received a liquid ethanol diet that was nutritionally balanced and provided 35% of calories in ethanol, beginning on day 6 of gestation. Control animals were pair-fed the same diet except that maltose-dextrins were substituted for ethanol. At birth pups of both ethanol-exposed and pair-fed groups were fostered by surrogate mothers which received normal rat chow ad libitum. An average of eight alcohol-exposed and eight pair-fed pups were killed at 0-1, 5, 7, 10, 14, 21, 28, and 42 days. Their fixed cerebella were bisected in the midvermal plane and one-half embedded in Araldite. Thin sections were cut from lobules II/III and stained with uranyl acetate and lead citrate and visualized with the electron microscope to evaluate the effect of ethanol on Purkinje cell growth and maturation. Although the basic layering of the cerebellar cortex was not altered, alignment of Purkinje neurons to form a monocellular layer was delayed associated with disorientation of some neurons in the ethanol-exposed pups. Delayed differentiation of Purkinje neurons in the experimental animals was also noted as evidenced by the ribosomal accumulation at the basal aspect of the cell at 14 days postnatally, resembling a 7-day control pup. Purkinje neurons of control pups were well differentiated at 14/21 days, with a centralized nucleus surrounded by a cytoplasm containing Nissl bodies, numerous Golgi complexes, and mitochondria. The ethanol-exposed pups at 14/21 days showed delayed maturation indicated by a basal ribosomal mass, with few segments of rough endoplasmic reticulum. At 28/42 days the Purkinje neurons of the controls showed a greater degree of differentiation and maturation in contrast to the reduced protein-synthesizing machinery, i.e., poorly developed endoplasmic reticulum and Nissl bodies, in the experimental pups. These studies showed delayed differentiation and maturation of Purkinje neurons as a consequence of ethanol exposure.

Abnormalities, Drug-Induced↗
PubMed1987

Altered Purkinje cell maturation in rats exposed prenatally to ethanol. II. Synaptology.

Pregnant rats of Sprague-Dawley strain were offered a protein- and vitamin-enriched nutritionally balanced liquid ethanol diet, providing 35% of calories as ethanol. Control animals were pair-fed identical liquid diet except that maltose-dextrins were substituted for ethanol. Pups of both ethanol-exposed and pair-fed groups were surrogate-fostered by mothers which received normal rat chow ad libitum. An average of eight pups of each experimental and control group was killed at 0-1, 5, 7, 10, 14, 21, 28, and 42 days. After fixation, their cerebella were bisected in the midvermal plane and one-half embedded in Araldite. Thin sections cut from lobules II/III were stained with uranyl acetate and lead citrate and the synaptology of the Purkinje neurons was studied with the electron microscope in both the experimental and control groups. Impaired climbing fiber maturation was seen in ethanol-exposed pups as evident from the presence of somatic spines--climbing fiber synapses at 14 days postnatally. In the 14-day-old control pups the climbing fiber maturation was complete or nearly complete as evident by their synapses on spines situated on the smooth dendritic branches and by the absence or paucity of climbing fiber--somatic spine synapse. In addition, a reduction in the number of parallel fibers was evident from the increase in Purkinje cell spines per varicosity in the ethanol-exposed pups. We conclude, therefore, a direct or indirect effect of ethanol occurs on climbing fiber maturation and Purkinje cell parallel fiber relationship.

Abnormalities, Drug-Induced↗
PubMed1986

Prenatal ethanol exposure and cerebellar development in rats.

Rats of Sprague-Dawley strain were fed a liquid ethanol diet that was nutritionally balanced and provided 35% of calories as ethanol. Control animals were pair-fed and received the same liquid diet with maltose-dextrins substituting for ethanol. At birth the pups of both the experimental and control groups were fostered by surrogate mothers which received normal rat chow ad libitum. An average of eight alcohol-fed and eight pair-fed pups were killed at 0-1, 5, 7, 10, 14, 21, 28, and 42 postnatal days. The fixed cerebella of these pups was bisected in the midvermal plane and one-half was embedded in paraffin and the other in Araldite. Projection drawings of hematoxylin and eosin-stained paraffin sections were made at 50X magnification. Using the graphics plate of an Apple II computer, the circumference and area of the vermal cerebellum was determined. We found that at all the time sequences studied the area and circumference of the cerebellum were significantly reduced in ethanol-exposed pups compared with the pair-fed controls.

Animals↗
PubMed1986

Growth patterns of rat body, brain, and cerebellum in fetal alcohol syndrome.

Pregnant Sprague-Dawley rats were offered protein- and vitamin-enriched, nutritionally balanced, liquid ethanol diet, providing 35% of calories as ethanol, beginning on day 6 of gestation. Control animals were pair-fed identical liquid diet except that maltose-dextrins were substituted for ethanol. At birth the pups of both ethanol exposed and pair-fed mothers were surrogate-fostered by normal dams. Plasma concentrations of ethanol and thyroxine were determined in dams of experimental and control groups. Thyroxine concentrations were significantly reduced in ethanol-fed dams compared with pair-fed. Pups of both groups were killed at 0-1, 5, 7, 10, 14, 21, 28, 35, and 42 postnatal days. The crown-rump, crown-tail lengths, and weights of body, brain, and cerebellum were significantly reduced in ethanol-exposed pups compared with controls at all time sequences studied.

Animals↗
PubMed1983

Neuronal changes induced by neonatal hypothyroidism: an ultrastructural study.

The postnatal development of the neurons of the cuneate nucleus was examined ultrastructurally in euthyroid and hypothyroid rats from birth to the sixth postnatal week. In the euthyroid animals, the neurons at birth displayed mild nuclear invaginations and a scanty cytoplasm with few organelles. By 2 weeks, there was a considerable increase in Nissl bodies. At 3 weeks, the neurons contained short lamellar arrays of endoplasmic reticulum. Between 3 and 6 weeks there was a reduction in the Nissl substance. In the hypothyroid animals, although the sequence of maturational changes generally resembled that of the controls, a number of differences were noted. The neurons at 1 week displayed dilations of perinuclear space, rough endoplasmic reticulum, Golgi complexes, and mitochondria. At 4 weeks both perikaryon and myelinated axons contained glycogen. Several neurons with cytoplasmic inclusions considered to be nonfunctional RNA were seen. The 6-week hypothyroid neuron exhibited large, clear, cytoplasmic vacuoles associated with a drastic reduction in cytoplasmic organelles. Presynaptic terminals showed a 50% reduction in mitochondrial numbers associated with the presence of glycogen granules. Three changes observed in neurites in all the age groups included: (1) large accumulation of glycogen in presynaptic terminals; (2) clear vacuoles; and (3) the presence of numerous lamellar bodies within reactive axons. Aberrant myelination, such as a single myelin sheath enclosing multiple processes, and instances of collapsed and redundant myelin were encountered.

Animals↗
PubMed1981

Astrocyte cell lineage. I. Astrocyte progenitor cells in mouse neopallium.

The astrocyte cell lineage during postnatal development of the neopallium of Swiss mice was studied, using a colony culture assay method in which dissociated neopallial cells form discrete colonies in culture. It was found that immature epithelial-like cells that from type A colonies in culture come primarily from the subventricular zone but also from other regions of the neopallium. In culture, cells of type A colonies from type C colonies consisting of cells, which although still epithelial like, differ morphologically from the type A colony-forming cells. In the presence of dibutyryl cyclic adenosine monophosphate (dBcAMP) the type C colonies form cells rich in glial fibrillary acidic protein (GFAP) and stainable with Cajal's gold chloride sublimate, a stain specific for astrocytes. Therefore, it is proposed that type A colony-forming cells are astrocyte progenitor cells resembling the "pale" cells found in the subventricular zone (Blakemore and Jolly, '72), the "large glioblasts" (Sturrock, '76) and the free subependymal cells (Privat, '70; Paterson et at., '73) in the corpus callosum. The sequence of the lineage, i.e., cells forming type A colonies give rise to cells forming type C colonies which eventually differentiate into astrocytes, takes place in situ as well as in culture. As postnatal development of the neopallium progresses the number of colony-forming cells decreases in the subventricular zone and in other parts of the neopallium. The astrocyte progenitor cells migrate from the subventricular zone to other parts of the neopallium and progress through the lineage of differentiation in all regions of the neopallium.

Animals↗
PubMed1978

Intranuclear inclusions in the developing neurons of the rat cuneate nuclei.

The ultrastructure of intranuclear rodlets, microtubules, fibrillar lattices and membranous inclusions found in the developing cuneate nuclei of rats is described. Rodlets, ranging in diameter from 96--312 nm and in length from 1--2 micrometer, are made up of tightly packed straight filaments measuring 5--8 nm in diameter. Microtubules with a diameter of 26 nm are clustered together. Fibrillar lattices are made up of fibrils with a diameter of 9 nm arranged in layers or sets. Two to nine sets make up a lattice, with a maximum width of 68 nm, in which the adjacent sets are arranged at an angle to each other. Rodlets and fibrillar lattices occur in 6.8% of the neurons. Membranous inclusions, reported here for the first time in normal neurons, are of 2 types: small vesicles of 0.1--0.6 micrometer and large vacuoles measuring 1--2 micrometer. Both types are bounded by either a single or a double membrane and generally have an electron lucent content. Membranous inclusions occur in 25.3% of the neurons. Changes in the frequency of occurrence of the various intranuclear inclusions in the course of postnatal development are also reported.

Animals↗
PubMed1978

Ultrastructural study of the persistence of colchicine-induced cytological changes in Harding-Passey melanoma.

Electron microscopic observations were undertaken on Harding-Passey melanoma in control tumors, colchicine-treated tumors, and tumors that were passed through five transplantations in mice subsequent to colchicine treatment. The untreated Harding-Passey melanoma tumor was composed of pleomorphic cells the cytoplasm of which contained tubulovesicular mitochondria and numerous free and membrane-attached ribosomes. Type A virus particles were observed in both mitotic and interphase cells. Colchicine-treated tumors exhibited several typical colchicine mitotic cells arrested in metaphase. A most significant feature of the colchicine administration was the appearance of microfilaments in both interphase and mitotic cells, a feature not observed in cells of the untreated tumor. Electron microscopy of colchicine-treated tumors carried through five transplantations at biweekly intervals revealed the presence of microfilaments in tissues fixed at each of the transplantations. It therefore appears that the cytological effects of colchicine resulting in the appearance of filaments in melanocytes of the Harding-Passey melanoma are more enduring than they were initially presumed to be.

Animals↗
PubMed1977

Postnatal development of mitral cell perikaryon in the olfactory bulb of the rat. A light and ultrastructural study.

The differentiation of the mitral cell perikaryon in postnatal rat olfactory bulb was studied with the light and electron microscope. At birth the mitral cell was distinguishable and occupied a definitive position in the mitral cell layer. The cell contained a large oval nucleus surrounded by a thin rim of cytoplasm. Ribosomes, free and clustered, were scattered in the cell cytoplasm. Rough endoplasmic reticulum was relatively scarce. The Golgi complexes were made up of stacks of smooth-surfaced cisternae and associated vesicles. In certain cases the Golgi complexes projected into cellular processes. Mitochondria were present in all regions of the cytoplasm and contained well developed cristae. At the end of the first week, the mitral cell had developed significantly in size, and the cytoplasm contained well-developed rough endoplasmic reticulum. The Golgi complexes were made up of several stacks of smooth-surfaced cisternae with the association of vesicles and electron dense bodies. The apical dendrites of mitral cells at this period had increased significantly in length. Subsequently, during the second and third week, the rough endoplasmic reticulum and Golgi complexes became well developed. Associated with the Golgi complexes were electron dense lysosomal bodies. At three weeks and in older cells it was observed that dense lipofuschin granules increased significantly. It is suggested that the mitral cell matures and differentiates earlier than cells in the cerebral cortex.

Animals↗