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Biomedical subjects

W Singer

Publications and source records attributed to W Singer.

At least 199 records · Page 11Linked to original sources

Acidophil stem cell adenoma of the human pituitary: clinicopathologic analysis of 15 cases.

In material of 347 surgically removed pituitary adenomas, 15 tumors (4.3%) were diagnosed as acidophil stem cell adenomas. These are immature neoplasms, assumed to derive from the common progenitor of growth hormone and prolactin cells, and usually containing both hormones by the immunoperoxidase technique. Clinically, they are regularly associated with hyperprolactinemia. Some patients may exhibit physical stigmata of acromegaly without biochemical evidence of the disease ("fugitive acromegaly"). The entity is also characterized by (1) relatively short clinical history; (2) large (grade III--IV), locally invasive adenoma, and (3) relatively low hormonal activity. By electron microscopy, these tumors are unicellular with immature cytoplasm, exhibiting some features of adenomatous growth hormone and prolactin with immature cytoplasm, exhibiting some features of adenomatous growth hormone and prolactin cells and frequently mitochondrial abnormalities as well. They are more aggressive than the well-differentiated adenomas of the "acidophil" cell line--a fact to be considered in postoperative management.

Adenoma, Acidophil

Topographic organization of orientation columns in the cat visual cortex. A deoxyglucose study.

Three-dimensional reconstructions of the orientation column system were obtained from the visual cortex of four cats using the deoxyglucose technique. One cat had normal visual experience, one was monocularly and two had selective experience with vertical and horizontal contours, respectively. In areas 17 and 18 orientation columns form a remarkably regular system of equally spaced parallel bands whose trajectory is orthogonal to the borderline between areas 17 and 18. This topographic organization is resistant to manipulations of early visual experience.

Animals

Restriction of visual experience to a single orientation affects the organization of orientation columns in cat visual cortex. A study with deoxyglucose.

In six dark reared, 4-weak-old kittens visual experience was restricted to contours of a single orientation, horizontal or vertical, using cylindrical lenses. Subsequently, the deoxyglucose method was used to determine whether these artificial raising conditions had affected the development of orientation columns in the visual cortex. After application of the deoxyglucose pulse one hemifield was stimulated with vertical, the other with horizontal contours. Thus, from interhemispheric comparison, changes in columnar systems corresponding to experienced and inexperienced orientations could be determined. The following results were obtained: (1) Irrespective of the restrictions in visual experience, orientation columns develop in areas 17, 18, 19 and in the visual areas of the posterior suprasylvian sulcus. (2) Within area 17, spacing between columns encoding the same orientations is remarkably regular (1 mm), is not influenced by selective experience and shows only slight interindividual variation. (3) In non-striate areas the spacing of columns is less regular and the spatial frequency of the periodicity is lower. (4) The modifiability of this columnar pattern by selective experience is small within the granular layer of striate cortex but substantial in non-granular layers: Within layer IV columns whose preference corresponds to the experienced orientation are wider and more active than those encoding the orthogonal orientation but the columnar grid remains basically unaltered. Outside layer IV the columnar system is maintained only for columns encoding the experienced orientations. The deprived columns by contrast frequently fail to extend into non-granular layers and remain confined to the vicinity of layer IV. (5) These modifications in the columnar arrangement are more pronounced in striate cortex than in nonstriate visual areas and, within the former, more conspicuous in the central than in the peripheral representation of the visual field. It is concluded that within layer IV the blue print for the system of orientation columns is determined by genetic instructions: first order cells in layer IV develop orientation selectivity irrespective of experience whereby the preference for a particular orientation is predetermined by the position in the columnar grid. Dependent on experience is, however, the expansion of the columnar system from layer IV into non-granular layers. It is argued that all distortions following selective rearing can be accounted for by competitive interactions between intracortical pathways, the mechanisms being identical to those established for competitive processes in the domain of ocular dominance columns. It is proposed that such experience dependent modifiability of connections between first and second order cells is a necessary prerequisite for the development of orientation selectivity in cells with large and complex receptive fields.

Animals

The effects of early visual experience on the cat's visual cortex and their possible explanation by Hebb synapses.

1. Kittens were dark-reared until 4-6 weeks old, and then for another 4-7 weeks with various combinations of cylindrical lenses, monocular occlusion, and normal vision. 2. Single unit recordings from 816 neurones of the visual cortex (area 17) were obtained after the end of exposure. Clear-cut effects on the distributions of the neurones' ocular dominance and orientation preference were found yielding close correlations with the rearing conditions. 3. It was confirmed that most cortical neurones prefer vertical stimulus orientations when experience is restricted to vertical contours in both eyes. It was further confirmed that, if the experienced orientations are different in the two eyes, each eye dominates over those neurones whose orientation preference corresponds to the orientation this eye has experienced. 4. When one eye is covered while the other sees only contours of one orientation, the ocular dominance distribution of cortical neurones shows a bias towards the open eye. Neurones dominated by this eye prefer orientations corresponding to the experienced range. Neurones preferring other orientations are shared between both eyes. 5. When vision is unimpaired in one eye and restricted to vertical contours in the other, binocularity is common among neurones preferring vertical orientations. Neurones with orientation preferences off the vertical are mainly monocular and dominated by the eye with unrestricted vision. 6. When normal monocular vision of one eye precedes restricted monocular vision of the other eye, only a few binocular units are encountered. Reversal of the initial effects of monocular experience is found only in neurones preferring the orientation that has been experienced by the newly opened eye. The other neurones remain dominated by the originally open eye. Thus, complementary distributions of orientation preferences are found for the two eyes. 7. A good correlation was found between the amount of orientational experience as determined by the number of orientations exposed and the number of normally tuned neurones. Conversely, the number of neurones responding to all orientations decreases with increasing amount of experience.

Animals

Functional amblyopia in kittens with unilateral exotropia. I. Electrophysiological assessment.

In two cats in which surgically induced, unilateral divergent strabismus had led to behaviourally determined amblyopia, a variety of electrophysiological parameters were determined in search of neuronal correlates of squint amblyopia. Tests that assess global neuronal excitability along the pathways from the two eyes to the visual cortex (areas 17 and 18) failed to reflect the functional inferiority of the squinting eye: retinographic responses and cortical evoked potentials elicited by Ganzfeld-stimulation and by stimulation of the optic nerves were identical for the two eyes. The ocular dominance distribution of neurons in area 17 showed the expected disruption of binocularity but failed to provide clear evidence for a functional inferiority of the squinting eye. At other levels of analysis, however, a clear difference between the two eyes was apparent: 1. Responses to optimally aligned light stimuli tended to be more sluggish and the under-representation of neurons with vertically oriented receptive fields was more pronounced in neurons driven from the deviated eye than in cells dominated by the normal one. 2. Interocular inhibition as assessed from electrically evoked potentials was found to be asymmetric; responses evoked from the amblyopic eye were suppressed more readily and over longer periods by conditioning shocks applied to the normal nerve than vice versa. 3. Numerous abnormalities reflecting the functional inferiority of the squinting eye became apparent in cortical potentials evoked by phase reversal of gratings of variable spatial frequency and contrast. A laminar analysis of these field potentials suggests impaired transmission along the intracortical pathways which relay activity to supragranular layers as a major cause for abnormal responses from the squinting eye. It is concluded that squint amblyopia is associated with a variety of neuronal changes at various levels of the visual levels of the visual system, the present data providing evidence for alterations at the cortical level.

Amblyopia

Functional amblyopia in kittens with unilateral exotropia. II. Correspondence between behavioural and electrophysiological assessment.

In two dark reared, 40 day old kittens unilateral divergent squint was induced be resecting the insertion of the medial rectus muscle. Behavioural testing revealed that the kittens used only the normal eye for fixation. Contrast sensitivity functions of the two eyes had visual acuity were determined behaviourally in a jumping stand whereby the kittens had to discriminate sine-wave gratings or variable spatial frequency and contrast from a flux equated homogeneous field. At photopic luminance levels the deviated eye showed a significant deficit in both kittens. This impairment was apparent over the whole range of spatial frequencies (0.18-0.99 c/deg) except for the lowest spatial frequency in one kitten. The interocular difference of visual acuity disappeared at scotopic luminance levels. In subsequent electrophysiological experiments contrast sensitivity functions were determined from cortical evoked potentials that were elicited by phase reversing square wave grating. Comparison between behavioural and electrophysiological results revealed a very good correspondence between the two sets of data. It is concluded that exotropia without alternating fixation leads to functional amblyopia of the deviated eye.

Amblyopia

The "vertical effect" in human squint amblyopia.

Grating acuity was tested in seven squint amblyopes as a function of orientation. In the squinting eyes of six unilateral amblyopes, the resolution for vertical gratings was much lower (by about 1/2 octave) than that of horizontal gratings. The non-amblyopic eyes of these subjects showed a normal "oblique effect". In one bilateral amblyope the selective loss of resolution for vertical contours was found in both eyes. This effect is well correlated with the reduced incidence of cortical cells encoding vertical contours in squinting cats. Both findings can be interpreted as an adaptive modification of the central visual system to alleviate the selective doubling of the vertical contours caused by strabismus.

Amblyopia

Correlative ultrastructural morphometry of human prolactin-producing adenomas.

Ultrastructural morphometry was applied to 24 surgically removed human sparsely granulated prolactin cell adenomas in an attempt to correlate the measurements with blood prolactin levels, size of tumour, and age and sex of patient. No correlation was apparent. However, further evaluation revealed that correlation existed between size of tumour and blood prolactin levels, indicating that tumour mass, and not subcellular morphology, was related to the amount of prolactin released.

Adenoma

Leydig-like cells in the adrenals of a woman with ectopic ACTH syndrome.

A 36 year old woman with hypercorticism and markedly elevated blood ACTH levels underwent pituitary ablation because of suspected hypophysial Cushing's disease. Since no adenoma was detected in the anterior lobe and the hypercorticism persisted, a bilateral adrenalectomy was performed. Four months later lymph node and mediastinal metastases of an anaplastic small cell carcinoma, with the presence of argyrophil granulation, as well as immunoreactive 19-39ACTH, beta-LPH and alpha-endorphin, were found. The primary site of ectopic ACTH production was not revealed. A light and electron microscopic study of the adrenals, in addition to cortical hyperplasia, disclosed numerous small cells associated with nonmyelinated sympathetic nerve fibers and containing cytoplasmic inclusions indistinguishable from Reinke crystals. The Leydig-like cell-nonmyelinated nerve complexes, noted in both the adrenal cortex and medulla, showed perivascular localization, and their morphologic features were similar to those of hilus cells of the ovaries or extraglandular Leydig cells of the testis. The underlying mechanism accounting for the development of Leydig-like cells remained obscure; cytodifferentiation from pluripotent mesenchymal cells, possibly mediated by secretory products of sympathetic nerve fibers, may provide an explanation for their formation.

ACTH Syndrome, Ectopic

Phasic electrodermal responses after visual stimulation in the cortically blind hemifield.

Phasic electrodermal responses were recorded after presenting targets within the blind part of the visual field to patients with damage to the geniculostriate pathway. The results suggest that the electrodermal component of the orienting response can also be elicited after damage to the visual cortex. The electrodermal responses are interpreted in terms of registration of a visual stimulus. This registration seems to be mediated by extrastriate pathways.

Dominance, Cerebral

Pituitary adenomas in old age.

Pituitaries obtained at unselected autopsies of 152 men and women over 80 years of age, dying of different diseases, have been investigated histologically by using various staining procedures, including the immunoperoxidase technique. In 20 pituitaries, 22 adenomas were found providing evidence that these tumors are common in aging subjects. In 9 adenomas out of 17 cases, the immunoperoxidase technique revealed the presence of prolactin, indicating that prolactin-producing adenomas constitute the most frequently occurring pituitary tumor type in old age. The presence of growth hormone was demonstrated in one adenoma which also contained prolactin. No storage of ACTH, FSH, LH or TSH was found in the tumors. The biologic behavior of pituitary adenomas disclosed as incidental findings in old age remains to be elucidated. These neoplasms may have a slower growth rate, but more work is required to establish whether they differ from those found in younger age groups.

Adenoma

Monocular activation of visual cortex in normal and monocularly deprived cats: an analysis of evoked potentials.

The unilaterally induced patterns of prominent excitatory post-synaptic activity within Areas 17 and 18 were investigated in normal and monocularly deprived cats. They were elicited by electrical stimulation of the optic nerves and evaluated with the one-dimensional current source-density method. 1. In Area 18 of normal cats the unilaterally and bilaterally induced current source-density patterns closely resemble each other. None of the mono-, di- or tri-synaptic activities is potentiated by binocular convergence. 2. In Area 18 of monocularly deprived cats the synaptic currents elicited by stimulating the nerve on the deprived side lead to approximately the same spatial and temporal distribution of sinks and sources as those induced from the normal eye; but the amplitudes are considerably smaller. This reduction is similar for mono-, di- and trisynaptic responses which indicates (a) that the imbalance between activity from the deprived and non-deprived eye is mainly due to reduced input to the cortical target cells from the deprived eye and (b) that the activity from the deprived eye still relayed to these cells is passed on to supra- and infragranular layers without diminution and in the same way as activity from the normal eye. 3. The imbalance of afferent activity from the deprived and non-deprived eye is apparent in the evoked potentials recorded from the white matter. This indicates that activity from the deprived eye is already strongly reduced in the thalamo-cortical fibres. 4. In monocularly deprived, but not in normal cats the monosynaptic activities from the two eyes are often segregated in depth within layer IV. 5. In Area 17 of both normal and deprived cats only a small fraction of the potential monosynaptic activity can be elicited by electrical stimulation of the optic nerves because of transmission failure in the lateral geniculate nucleus. Comparison of the current source-density patterns elicited from the normal and deprived nerve in monocularly deprived cats indicates that activity produced by fast conducting afferents is more affected (reduced) by deprivation that that conveyed by slower afferents.

Animals

Silent corticotropic adenomas of the human pituitary gland: a histologic, immunocytologic, and ultrastructural study.

Among 300 surgically removed pituitary adenomas, 17 tumors containing immunoreactive 1-39 adrenocorticotropin (ACTH) and/or 19-39 ACTH, beta-lipotropin, and alpha-endorphin but unassociated with clinical signs of Cushing's disease have been detected. These neoplasms were divided into basophilic adenomas with strong periodic acid-Schiff (PAS) and lead-hematoxylin positivity and chromophobic tumors with moderate or no PAS and lead-hematoxylin positivity. The former were densely granulated tumors with a fine structure strikingly similar to that of functioning corticotropic cell adenomas. The latter were sparsely granulated with varying ultrastructural patterns. The marked morphologic diversity suggests that these adenomas, despite their similar immunocytologic characteristics, represent more than one entity. Clinically, the most common finding was a rapidly progressing visual defect. An unusually high incidence of infarction (5 cases) and recurrence (5 cases) was noted, underlining the importance of correct morphologic diagnosis and careful follow-up.

Adenoma

Excitatory synaptic ensemble properties in the visual cortex of the macaque monkey: a current source density analysis of electrically evoked potentials.

The spatio-temporal distributions of excitatory synaptic ensemble activities in A17 and A18 of the visual cortex of the macaque monkey have been investigated. The synaptic activities were elicited by electrical stimulation of the primary efferents and were localized by applying the current source density analysis to the intracortically recorded field potentials. The principal results are as follows: 1. In A17, two groups of activity, evoked by fast and slow afferents, respectively, were distinguishable. 2. The fast afferents induced monosynaptic activity in layer IV C alpha and layer VI, disynaptic activity in layer IV C alpha and in the supragranular layers and trisynaptic activity in layer IV B. 3. The slow efferents induced monosynaptic activity in lower layers IV C beta and layer VI, disynaptic activity via strong connections in upper layer IV C beta, further disynaptic activity in layers III and IV B and trisynaptic activity in layers V A and II. 4. With the exception that the CSD data reveal more polysynaptic activity within layer IV, there is good agreement between the spatio-temporal distribution of synaptic activities and the cortical circuit diagrams proposed in anatomical studies. 5. In A18, activities from the slow and fast conducting afferent systems are revealed in layer IV, both most likely mediated by the monosynaptically activated target cells of A17. These activities are passed on to the supra-and infragranular layers. 6. In the lateral geniculate nucleus the safety factor of transmission is higher for activity conveyed by slow-than by fast-conducting retinal afferents. 7. The spatial distribution of monocularly evoked surface potentials failed to reveal the ocular dominance columns. 8. Comparison with the cat indicates that, with respect to the intracortical circuitry and LHN-transmission, there are more similarities between the fast-group activity in the monkey and the y-system in the cat and between the slow-group activity in the monkey and the x-system in the cat than vice versa.

Animals