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Notes: Zusammenfassung Die Fähigkeit des Hörorgans zur zeitlichen Auflösung kurzzeitiger Signalveränderungen bei monauraler oder binauraler akustischer Stimulation ist nicht nur im Hinblick auf Sprachverarbeitungsprozesse von wesentlicher Bedeutung, sondern betrifft auch die Lokalisation und Selektion im akustischen Umgebungsraum. In diesem Zusammenhang werden elektrophysiologische Untersuchungsergebnisse zur Evozierung spezifischer Reizantwortmuster aus dem primären akustischen Rinderprojektionsfeld AI der Katze bei kurzzeitiger interauraler Laufzeitveränderung vorgestellt. Die verschiedenen Neuronenpopulationen, die durch unterschiedliche Plazierung zweier Ableitelektroden erfaßt werden, deuten auf signifikante Unterschiede im Hinblick auf das Zeitauflösungsvermögen hin. Während für Klickstimulation beide Elektrodenkonfigurationen deutliche Potentialmuster aufweisen, wird für eine kurzzeitige Veränderung der interauralen Laufzeit nur für eine Elektrodenanordnung ein ausgeprägtes Reizantwortmuster evoziert. Dieses ist durch eine abnehmende Erregungsamplitude bei Verkleinerung der interauralen Laufzeitdifferenz und des untersuchten Zeitintervalls gekennzeichnet.

Notes: Summary Skin biopsies of patients with small and large plaque parapsoriasis, premycotic lesions and mycosis fungoides in different stages were examined. Special attention was paid to the relationships between Langerhans cells (LC) and the neighbouring keratinocytes and lymphocytes. At the contact areas of LC and keratinocytes as well as LC and lymphocytes, particular cell membrane phenomena were observed. Aggregations of Langerhans granules and fusions of granules with LC plasma membranes were found exclusively at LC-keratinocyte interfaces. At LC-lymphocyte contact zones cell membrane appositions were seen. In all cases investigated, virus-like particles were mainly ound in LC and indeterminate cells (IDC). In 3 cases lymphocytes also contained these particles. It was of particular interest that virus-like particles were observed in skin specimens of all diseases investigated. Discrimination of these particles from other cellular organelles - especially lysosomes- was difficult, however. The significance of our findings, particularly regarding to the supposed virus aetiology of cutaneous T cell lymphomas, is discussed.

Notes: Abstract A case of medullary type of nephrocalcinosis detected by ultrasound, is presented. Calcifications could also be demonstrated by CT scanning and were confirmed by percutaneous biopsy.

Notes: Summary A case of “nonsecretory” myeloma is described. The patient had typical osteolytic lesions and marked infiltration of myeloma cells in the bone marrow, and plasma cell leukemia. A good partial remission was obtained with Melphalan, but the patient relapsed and died one year later. Immunofluorescent and immunoelectroscopic studies on the myeloma cells demonstrated the presence of cytoplasmic γ-and κ-chains at the initial stage and of only κ-chains at a relapse. The electron microscopic method for polysome analysis indicated that both L-and H-chains were synthesized on membrane-bound polysomes initially, but the ability to produce H-chain was missing at the relapse.

Notes: Summary In order to evaluate whether or not the action of salmon calcitonin (sCT) at the kidney level could be mediated through specific receptors for the hormone, we have studied the effects of sCT infusions on urinary excretion of cyclic nucleotides in humans. Parallel in vitro studies have been conducted by evaluating the effects of sCT on cyclic nucleotide levels in primary cultures of cortical and medullary human kidney cells. In vivo experiments showed that sCT induced an increase in cGMP in human urine, which was rapid and short-lasting, being superimposable on the increase of urinary excretion of calcium and magnesium. The increase of inorganic phosphate urinary excretion was delayed and appeared to parallel that of urinary cAMP. On the other hand, our in vitro experiments showed that sCT stimulated the guanylate cyclase—cGMP system of human kidney cortical cells at nanomolar concentrations, while higher concentrations of the hormone were required to activate the adenylate cyclase—cAMP system. In addition, sCT was not able to significantly modify the cellular levels of either nucleotide in human kidney medullary cells. Present data demonstrated a direct effect of sCT on human kidney cortical cGMP production, while the efficacy of sCT on the kidney cortex adenylate cyclase—cAMP system appears to be delayed and/or reduced.

Notes: Summary Neurons responding to deep or cutaneous stimuli are situated in different parts of the ventrobasal complex. Within the cutaneous region elongated clusters of cells with common place and modality properties project to single columns in the somatic sensory cortex. The present study sought to determine to what extent single lemniscal axons contribute terminals to different regions and to different cell clusters. Lemniscal axons, anterogradely labelled by horseradish peroxidase injected into the medial lemniscus of cats were examined light and electron microscopically. Labelled axons bore one or two, mainly anteroposteriorly oriented, terminal ramifications. These ramifications were relatively small when compared to the length of the complex. Some of the axons bore one or two collaterals that ascended towards the dorsal edge of the complex and formed an additional small ramification there. Electron microscopic analyses of labelled lemniscal axons provided further evidence to that already available that most of their boutons synapse on proximal dendrites of relay neurons and on presynaptic dendrites, presumably belonging to interneurons. A concurrent study of Golgi-impregnated ventrobasal neurons showed three morphological types all with dendritic fields of similar extent. From measurements of the lemniscal terminal ramifications and the counting of counterstained cells it was calculated that 50–120 neurons may receive input from a single terminal ramification. However, because of the restricted extent of the ramifications, the elongated clusters of cells projecting to a single cortical column probably receive input from multiple lemniscal axons and not all members of the cluster receive inputs from the same axons.

Notes: Summary In alert cat and monkey, a unit type recorded in the region of the thalamic internal medullary lamina seems to provide the extraretinal signal postulated by Singer (1982) to explain the development of mature receptive field properties in cortical visual neurons. These thalamic units are silent (or silenced) during saccades in all directions; they discharge as soon as the eyes assume a new position. The abolition of this discharge by thalamic lesion, or conversely, its elicitation by electrical stimulation could respectively prevent or facilitate plastic changes in visual cortical areas of kittens.

Notes: Summary The retrograde fluorescent technique was used to label cortical neurons which project to both the caudate nucleus and also to the centromedian-parafascicular (CM-Pf) thalamic nuclear complex. After experimentation with many other pairs of fluorescent tracers, Evans Blue (EB) and Fast Blue (FB) were chosen as the best combination for studying the systems involved. Following injections of EB into the caudate nucleus and FB into the CM-Pf complex, doubly labeled medium-sized pyramidal neurons were present within layer V and VI of specific cortical regions. These cells were found on the inferior bank of the cruciate sulcus, in the anterior limbic area, in the cingulate and anterior sylvian gyri and within the buried cortex of the presylvian sulcus. The doubly labeled cells were relatively few in number compared to the more numerous singly labeled FB (corticothalamic) cells found in layers V and VI, and the very numerous singly labeled EB (corticostriatal) neurons, located in layers II, III, V, and VI.

Notes: Summary The relationship between orientation selectivity and spatial receptive field organization was analyzed. Receptive field maps were made with a dual stimulus technique where an optimally oriented activation slit was presented in the most responsive region to produce activity against which the effect of a test spot in various positions was determined. Both simple and complex cells had receptive fields which were subdivided into adjacent elongated and antagonistic subrogions. When the two stimuli were presented in phase (both ON or OFF simultaneously) the fields had a central enhancement region with a strong suppression flank on one or both sides. Optimal slit orientation was related to the location of the suppression flank relative to the location of the central enhancement region, and the degree of orientation selectivity to the shape of the subregions and the distance between them. Estimated orientation tuning curves calculated from the receptive field maps gave satisfactory first approximations to experimental curves. The relative contribution of enhancement and suppression to orientation selectivity was studied by presenting a test slit in different orientations in phase with an optimally oriented activation slit. The orientation selectivity was produced almost exclusively by the flank suppression indicating that orientation selectivity is produced by inhibitory input. The flank suppression lacked any specific orientation selectivity, and it occurred only when both the central region and the flanks were activated in phase. Orientation selectivity in both simple and complex cells is explained by a receptive field organization where the cells have input from partially overlapping excitatory and inhibitory fields which have their centers slightly displaced from each other.

Notes: Summary This report describes two types of reticular epithelial cell in the thymic cortex of the BALB/c mouse, an immature and a mature form. During early stages of lymphoma development, i.e., 2–6 weeks postinfection (p.i.) with Moloney leukemia virus (M-MuLV), activation of the epithelial cells is observed. Although the percentage of these cells in the total cell population of the thymic cortex remains constant during that time, the number of mature epithelial cells is significantly increased in infected animals. Subsequently, about 6 weeks p.i., the number of immature epithelial cells starts to increase, whereas the number of mature reticular epithelial cells declines and the appearance of the mature epithelial cells changes drastically. The results of light and electron microscopic studies indicate degeneration of the mature reticular epithelial cells at the onset of lymphoma development at a time when the first deficiencies in the immunologic competence of the reticular epithelial cells are apparent.

Notes: Summary Sixteen cases of typical highly malignant osteosarcoma were investigated by light, electron, and immunofluorescence microscopy to demonstrate the presence of collagen types I–III. It was shown that, in light-microscopically anaplastic areas of the tumor, collagen type III predominates, while only very few membranes of collagen type I are observed. Ultrastructurally, the cells are characterized by numerous free ribosomes in their cytoplasm and only a few membranes of granular endoplasmic reticulum (ER). In osteoblastic areas, collagen type I is increased, while type-III collagen is decreased. The cytoplasm of cells contains markedly more granular ER. An increasing mineralization of matrix is observed. In fibroblastic areas of the tumors, collagen types I and III are codistributed. Tumor cells have a fibroblast appearance with elongated nuclei and well developed granular ER. The chondroblastic areas, characterized by immature neoplastic cartilage, contain varying amounts of collagen type II. Chondroblast-like tumor cells have typical ring-shaped membranes of granular ER in their cytoplasm. The evidence of different collagen types in osteosarcomas lends additional support to the concept that a pluripotent mesenchymal cell is the stem cell of osteosarcomas.

Notes: Summary 65 cases of hemangioendothelioma (HE) of the thyroid were accepted as such after control of slides of surgical or autopsy specimen or both. In a few of the more recent cases material could be examined by electron microscope and in some the search for factor VIII-related antigen (FVIIIRAG) was carried out. The demonstration of Weibel-Palade bodies in tumour cells in two cases and the evidence of FVIIIRAG in tumour cells of at least two cases, including primary tumour and distant metastasis, finally show, that the hemangioendothelioma of the thyroid is not simply an anaplastic carcinoma with some peculiar features; at least some of these tumours are true endotheliomas. The proposal that the term hemangioendothelioma be eliminated from the classification of thyroid tumours is therefore unfounded.

Notes: Summary An ultrastructural comparison of 7 examples of myxoid malignant fibrous histiocytoma (myxoid MFH) with 6 of myxoid liposarcoma is described. Despite certain histological differences between the two, electron microscopy was more valuable in differentiating MFH from liposarcoma. Electron microscopically, MFH contained a variety of cell types including histiocyte-like, fibroblast-like, intermediate-type, xanthomatous, multinucleated tumor giant cells and undifferentiated cells. Liposarcoma was composed mainly of lipoblasts at various stages of differentiation with a minority of undifferentiated cells and fibroblast-like cells. In contrast to the component cells of the MFH, these lipoblasts were characterized by abundant cytoplasmic glycogen, numerous pinocytotic vesicles and a discontinuous basal lamina in addition to large lipid droplets.

Notes: Summary The author reports on the electron-microscopic examination of the diffuse tracheobronchial amyloidosis of a 51-year-old patient. The amyloid deposits were located in the lamina propria of the tracheal and bronchial mucosa. At the edge of the nodular deposits, condensation and radial arrangement of amyloid fibrils could be seen. Closely connected with the amyloid, active fibroblasts were present and their cytoplasm contained amyloid fibrils. The cell membrane of the fibroblasts was missing in part. Intracellular amyloid fibrils mingled with extracellular deposits. It can be assumed that active fibroblasts play an important role in local amyloid formation.

Notes: Summary A quantitative analysis was carried out on the thalamic ventrobasal (VB) complex of the cat. The following numerical and metrical parameters of the neuronal elements (cells and fibers) were determined: 1. Volume of nucleus: 27.38 mm3 2. Total number of neurons: 243,000 3. Total number of fibers of medial lemniscus: 26,000 4. Volume of arborization space of one lemniscal fiber: 2.26×106 μm3. Numerical data of relay neurons and lemniscal fibers and their relations as basic factors in the estimation of the degree of divergence and convergence of lemniscal input were calculated and compared. It was found that the probable degree of convergence is four-fold (1–4) and of divergence 27-fold (1–27) with regard to the relationship of fibers and cells in the VB. The quantitative data obtained in the VB and our considerations on convergence and divergence were compared with analogous values obtained for the lateral geniculate body LGB. The differences between the two sensory relay nuclei reflect differences in their modes of impulse transmission.

Notes: Summary The microvascular architecture of cat uteri from the 22nd to the 62nd day of pregnancy was investigated on corrosion casts by means of scanning electron microscopy. These findings, concerning the endometrial labyrinthine zone, were compared with those on corresponding semithin histological sections. Each area in the zonary girdle of feline placenta is supplied by a centrally located stem-artery. Such a stem-artery displays branching vessels, which partly anastomose with other areas, and originates from the superficial arterial network of the uterus. It straightly crosses the myometrial and labyrinthine layers and branches several times, forming a funnel-shaped system on the fetal side of the labyrinth. Arterioles ramifying from this system enter the septal capillary network of the labyrinthine zone which is composed of single lamellae with progressively complex shapes during pregnancy. This network is oriented in feto-maternal direction. Venules, originating at the end of an area, converge from the lamellae to stem-veins. These veins link the labyrinth and deep endometrial layers with a venous plexus in the myometrium, which, finally, joins the superficial network of uterine veins.

Notes: Summary The brain of an autopsy case of Menkes' kinky hair disease (MKHD), after routine histological examination, was studied extensively by electron microscopy, particularly the mitochondrial alterations. There were widespread mitochondrial abnormalities, including enlargement with tubulo-vesiculated cristae, swelling, and dense body formation and occasional accumulation of glycogen within mitochondria, in addition to increased numbers of mitochondria in some neurons. These abnormalities of mitochondria were present in decreasing severity in the following: Purkinje cells, neurons of the molecular and granule cell layers of the cerebellum, and neurons of the cerebral cortex, globus pallidus, lateral nuclei of the thalamus, caudate nucleus, and the myelinated axons in the white matter. This distribution and the degree of mitochondrial abnormalities in the various structures of the brain were compared with those of degenerative lesions in the respective structures. The comparison disclosed that there was a positive correlation between the two. The mitochondrial enlargement and swelling as in the present study had been well documented in the brain of the brindled mouse; mitochondrial dense bodies had also been reported in previous case reports of MKHD by other authors. The present study strongly suggests that the mitochondrial disease is an essential abnormality and may be responsible for the progressive degeneration of the CNS in MKHD.

Notes: Summary An ultrastructural and morphometric study was performed on sural nerve biopsies of four industrial spray painters (35–59 years) and 11 controls (6–64 years). No difference could be shown in spray painters and age-matched controls as to the number of myelinated nerve fibres per area, their size distribution, variation of internodal length along single nerve fibres or the ratio between the number of myelin lamellae and the axon circumference. There was marked scattering of the two latter parameters in older exposed and control individuals. The distribution of NADH2-tetrazolium reductase activity was similar in exposed and control cases. The general ultrastructural appearance of nodal-paranodal regions in controls conformed with that noted in experimental animals. The overall ultrastructural organization and age-related changes of nerves of exposed cases were similar to those of control cases except for a presence of paranodal axonal mitochondria which contained glycogen-like particles in exposed cases. In one exposed case abundant dispersed or clustered glycogen-like particles were seen in the paranodal axoplasm. These findings are suggested to be an effect of chronic exposure to organic solvent vapours. Ageing seems, however, to have a much greater impact on the morphology of the sural nerve fibre than occupational exposure to organic solvent.

Notes: Summary The syndrome of arthrogryposis and palatoschisis (SAP), an inherited syndrome of muscular hypotonia in Charolais cattle, was used as an experimental model to study neuromuscular differentiation. The ultrastructural development of muscle, peripheral nerve, and neuromuscular junctions was studied to determine the sequence of events preceding hypotrophic changes in the skeletal muscles of affected calves at birth. Dorsiflexion of the metatarsophalangeal joints in the hindlimbs occurred in fetuses older than 3 months of age, but hypotrophic changes in skeletal muscle, manifested as small fibers scattered among larger and occasional degenerating fibers, was not apparent until late in gestation, affecting 8-month-old fetuses and neonatal calves. Electron microscope and enzyme histochemistry studies disclosed differentiation of skeletal muscle into fiber types which is consistent with changes expected from disuse and does not indicate a primary myopathic abnormality. Abnormal differentiation of neuromuscular junctions (NMJ), composed of several separated axonal endings terminating in shallow synaptic gutters, indicated impaired maturation of the synapse. The earliest indication of abnormal NMJ was observed in a 5-month-old SAP fetus. The clinical signs and pathologic changes found in the neuromuscular junction and skeletal muscle of SAP fetuses are consistent with an embryologic defect occurring during development of the central nervous system (CNS) that affects the integrated function of the motor neurons to the limbs. However, diversification of myofibers by histochemistry and ultrastructural parameters is evidence that the intrinsic physiologic properties of spinal motor neurons were retained.

Notes: Summary The electron-microscopical appearance of a Rathke's cleft cyst is described. The cyst lining is seen to consist predominantly of secretory columnar epithelium, both ciliated and non-ciliated. There are also epidermoid cells occurring singly or in squames. The histogenesis of Rathke's cleft cysts, in relation to craniopharyngiomas, is discussed.

Notes: Summary Neonatal rats received s.c. injections of methymercuric chloride (MeHg) in physiological saline (1.5 mg Hg/kg b.wt.) at 48-h intervals from postnatal day 2 to day 50. Littermate controls were injected with an equivalent volume of saline. All animals were perfused on day 51 and blocks of cerebral cortex were prepared for electron microscopy. Ultrastructural changes in mitochondria were evident in the dendrites, axons and presynaptic terminals of cortical neurones in the MeHg-treated animals. Many mitochondria were condensed with an increased electron density of the inner matrix. Some profiles exhibited regressive alterations, including a disruption of cristae and the inner membrane with an accumulation of electron-opaque material in the matrix. Membranous whorls were found in association with the most degenerate mitochondria. A morphometric analysis of mitochondrial profiles in the neuropil of layer I revealed a 24% decrease in average profile area and a 16% increase in the number of profiles per micrograph in the MeHg-treated animals. These pathological changes in mitochondrial ultrastructure are consistent with an inhibition of mitochondrial respiration. The observed increase in the number of mitochondrial profiles may reflect a compensation by cortical neurons for the reduced efficiency of aerobic metabolism in the individual organelle.

Notes: Summary Intrafusal and extrafusal nerve segments in muscle spindles from tumbricalis muscles of the hind-paw of the rat were studied by electron microscopy from 10h to 5 days after severance of the sciatic nerve. In several spindles examined, nerve fascicles piercing the spindle capsule in the equatorial region contained a large myelinated, a smaller myelinated and an unmyelinated fiber. Unmyelinated fibers were not present in small fascicles leading to the polar region. The changes in the extrafusal nerve segments followed the pattern of Wallerian degeneration. Intra-axonal glycogen deposits were prominent in sensory fibers. The unmyelinated fibers were the earliest to degenerate, the large myelinated ones the latest. Differences between motor and sensory fiber degeneration emerged in their preterminal intrafusal segments and were analogous to those of the nerve endings. Terminal nerve fibers in the spindle equator succumbed to attack of mesenchymal cells, leaving extensive basement membrane reduplications around myelin debris-laden Schwann cells, while polar fibers were engulfed by Schwann cell processes, leaving regular bands of Büngner.

Notes: Summary A case of adrenoleukodystrophy was studied morphologically and biochemically. The patient was a 28-year-old man with no family history of adrenoleukodystrophy. His neurologic symptoms were cerebellar ataxia, spastic paraplegia, pseudo-bulbar palsy, and a minimal visual disturbance, with neither adrenal nor hypogonadal symptoms. The morphological and biochemical findings in this case are identical with those in typical adrenoleukodystrophy, but the topographical distribution of the lesions is distinctly different. The changes selectively affect the white matter in the cerebellum and brain stem in contrast to minimal involvement of the occipital white matter.

Notes: Summary Thirty-three rectus superior extraocular muscles from 23 autopsy cases, all over 60 years, were examined. Eosinophilic inclusions (Hirano bodies) were observed in all the muscles; they were stained deep red by Masson's trichrome stain and were positive for protein stain. They consisted of a collection of filamentous structures of two types: (1) a regular array of filaments 100 Å in diameter which sometimes were arrayed in perpendicular planes and (2) another type in a herring bone or ladder-like pattern. Both structures were closely associated with the accumulated thin filaments 50–60 Å in diameter (actin?) in the subsarcolemma. The frequent appearance in aged muscle fibers of Hirano bodies indicates that their formation is a change closely related with aging.

Notes: Summary The construction of renal lobules in Triturus (Cynops) pyrrhogaster was studied by reconstruction from serial semithin sections, and the structure of nephrons, collecting ducts and ureters was investigated by means of light and electron microscopy. In T. pyrrhogaster the kidney was mesonephros in construction; renal lobules were arranged segmentally and each of them sent one ureter. Male ureters ran caudally and met together before joining the Wolffian duct. In renal lobules, long collecting ducts ran medio-laterally in the dorsal aspect of the kidney and sent several branches ventrally. Each branch duct or short collecting duct received one nephron. Each nephron had five segments; 1) renal corpuscle, 2) ciliated neck segment with or without a naphrostome, 3) proximal tubule, 4) ciliated intermediate segment and 5) distal tubule. Proximal and distal tubules were segregated spacially in renal lobules and occupied the peripheral and central zone respectively. The filtration barrier of the glomerulus consisted of both the basal lamina of podocytes and the subendothelial connective tissue, and was much thicker than the mammalian filtration barrier. Proximal tubule cells had a brush border, apical specialzation for reabsorption of organic materials and well-developed smooth endoplasmic reticulum, but few baso-lateral interdigitations. In distal tubule cells, baso-lateral interdigitations and infoldings were well-developed. Collecting duct cells had a sparse cytoplasm. Ureter cells in males contained many secretory granules. On the basis of structural organization of the newt kidney as well as physiological data in literature, we suggest that in land vertebrates proximal tubules were primarily adapted to reabsorption of organic materials and distal tubules to reabsorption of electrolytes and water.

Notes: Summary Distribution of serotonin nerve fibers in the hypothalamus of the cat was studied using the peroxidase antiperoxidase (PAP) immunohistochemical method. There was a heavy concentration of serotonin nerve fibers in the nucleus suprachiasmaticus, the nucleus ventromedialis and the nucleus dorsomedialis. The distribution pattern of the serotonergic fibers in the cat was principally similar to that of the rat and monkey. However, species differences were noted in the mamillary complex, the nucleus hypothalamicus anterior, the nucleus paraventricularis and the nucleus supraopticus.

Notes: Summary Human mesonephric duct epithelial cells contained empty appearing regions in the infranuclear cytoplasm when prepared for transmission electron microscopy using glutaraldehyde and osmium fixation. The same regions stained positively with PAS in Epon sections for light microscopy suggesting that glycogen was present. Incubation with saliva abolished the reaction. For electron microscopy the glycogen stained very intensely if a mixture of osmium tetroxide and potassium ferrocyanide was used instead of osmium alone. Glycogen accumulations were present between the ages of 5 to 10 weeks and absent at the age of 15 weeks. Reports by others indicate that glycogen may be present in different reactive forms in relation to its staining behaviour after various fixatives. The present results, and similar studies in other tissues, indicate that osmium tetroxide-potassium ferrocyanide fixative should be used routinely for preservation of embryos and fetuses and where indicated, for ultrastructural identification of glycogen and cytoplasmic filaments in clinical specimens.

Notes: Summary Immune complexes of horseradish peroxidase (HRP) and rabbit IgG antibodies to HRP were used to study the Fcγ-receptors in granulomas of cutaneous sarcoidosis. Cryostat sections of skin biopsies were incubated with HRP-anti-HRP, and the peroxidase activity was demonstrated with 3,3-diaminobenzidine tetrahydrochloride and H2O2. Most cells in the granulomas, both epithelioid and giant cells, were stained. By electron microscopy, the reaction products were localized to the plasma membranes of the cells as well-defined granular deposits. No reaction product was demonstrated intra- or extracellularly.

Notes: Summary Tissue from seven patients with tuberous sclerosis and subependymal giant-cell tumors was examined with special stains, immunohistochemistry, and electron microscopy. Immunoreactive glial fibrillary acidic protein (GFAP) was not found in the giant cells of four tumors, but was present in some tumor cells in the other three. Immunoreactive S-100 protein was present in tumor cells of six cases; it was also seen in more tumor cells than was GFAP. Electron microscopy was similar in all cases and showed that the tumor cells had numerous organelles — many dense bodies thought to be primary lysosomes, swollen mitochondria, Golgi complexes, rough and smooth endoplasmic reticulum, free ribosomes, and sparsely distributed intermeadiate filaments. In one case, neurosecretory granules, microvilli, and synapses were observed. In another subject, prominent, thick bundles of glial filaments were seen. These findings suggest that the tumor is made up of unique cells in addition to cells with recognizable neuronal or astrocytic features.

Notes: Summary Rats were exposed to 6.1 bar (abs.) air for 90 min and subsequently decompressed to the ambient pressure. After a decompression rate of 6.8 bar/min pial veins and superior sagittal sinuses were found to contain gas bubbles; no intravascular bubbles were observed subsequent to a decompression rate of 1.5 bar/min. Under the electron microscope platelet aggregates were observed at both the electron-dense layer of the blood-bubble interface and in pial veins with no bubbles. It is concluded that during decompression sickness bubbles and both activation and aggregation of platelets occur in intracranial veins. Subsequent venous congestion may contribute to the neuronal lesions and symptoms of acute decompression sickness.

Notes: Summary Five patients with pityriasis rubra pilaris (PRP) were analyzed by means of light and electron microscopy as well as by histochemistry and autoradiography. The results were compared with findings in psoriasis vulgaris. In PRP we found a moderate increase of the labeling index of epidermal cells, a highly increased labeling index of dermal infiltrating cells, and a mild spongiosis, and in the stratum granulosum, a decreased number of tonofilaments and an increased number of keratinosomes. The horny layer in PRP showed a pronounced histochemical and electron microscopical parakeratosis, even when histological parakeratosis was absent. In contrast with psoriasis vulgaris, there was no exocytosis of polymorphonuclear leucocytes into the epidermis, the papillomatosis index was normal, and there were no tortuous capillaries in the dermal papillae. The stratum granulosum was always present and sometimes thickened, showing electron microscopical changes different from those referred to in psoriasis. These changes point to a relatively distinct pattern of epidermal changes in PRP.

Notes: Summary A patient with acute lymphoblastic leukemia (ALL) with cells containing two types of cytoplasmic inclusions is described. The inclusions appeared as glubular bodies containing electron dense material with homogenous structure and as crystalloid formations confined in organelles with structure similar to that of the surrounding mitochondria. In distinction to other reports, these structures were not related to the endoplasmic reticulum. The possibility that some of them represented altered mitochondria is discussed.

Notes: Summary The renal function of a population of workers occupationally exposed to mercury in the chlor-alkali industry has been examined and compared to that of a population of workers with no occupational exposure to mercury. Measurement of specific urinary proteins and enzymes have been carried out on each individual on three separate occasions and have been complemented by blood plasma measurements at the final visit. Under the conditions of exposure to mercury sustained in this study, there is no evidence of an increased prevalence of renal dysfunction as indicated by enzyme and protein measurements. The urinary concentration of the low molecular weight protein, β 2-microglobulin, is significantly lower in the mercury-exposed group than in the control group. In contrast to recently published literature, no relationship is seen between urinary mercury concentration and the appearance of high molecular weight protein in urine. A small increase in the prevalence of higher activities of the urinary enzyme N-acetyl -β-glucosaminidase and gamma glutamyl transferase is observed when the urinary mercury concentration exceeds 100 μg/g creatinine. A small increase in the prevalence of raised urinary N-acetyl-β-glucosaminidase activity is observed when the duration of exposure to mercury exceeds ten years. The pattern of proteinuria has been characterised in a total of sixteen individuals from both populations; a low molecular weight proteinuria is seen in three individuals from the control group whilst a high molecular weight proteinuria is seen in the remainder (seven in the control and six in the mercury group).

Notes: Summary Cats with a natural convergent squint were discovered within a colony of normal Mill Hill cats. In two of them single unit recording was undertaken in area 17. The ocular dominance distribution showed a clear disruption of binocularity in both hemispheres. This lack of binocular units was comparable to cats with artificial, surgically-induced strabismus and differed significantly from the ocular dominance distribution of a normal control group. The existence of these natural, non-albino squinters strengthens the use of cats as an animal model for strabismic amblyopia.

Notes: Summary Residual neurons following chronic surgical disconnection from the cortex were studied by light and electron microscopy in the dorsal Lateral Geniculate Nucleus (LGN) of adult cats. One year after operation the volume of the decorticated LGN had shrunken to approximately half that of the control LGN. The number of nerve cells decreased at the same time, to 13–15% of the control, with relatively higher cell loss in A and A1 laminae than in lamina C. The Golgi, Golgi-EM and EM analysis of the residual neurons revealed that they contain two distinct nerve cell types. (1) 55% of all surviving neurons were identified as geniculo-cortical relay cells, while (2) 45% of the persisting nerve cells were interneurons. These data suggest that in the normal LGN of adult cat 7% (or more) of all nerve cells are local interneurons. Finally, those factors which might contribute to the unexpected survival of many relay neurons to the axotomy-caused retrograde degeneration, are considered and discussed.

Notes: Summary EMG responses, vertical and A-P shear forces and kinematics of “automatic postural responses” to unexpected translational perturbations in the headward and tailward directions were studied in cats. Muscles acting on the major joints of the forelimbs and hindlimbs were studied. Movement of the animals in response to perturbation were highly stereotyped and consisted of two phases: (1) motion of the feet during platform movement while the trunk remained relatively stationary followed by (2) active correction of posture by movement of the trunk in the direction of perturbation. Vertical force changes occurred after the perturbation was well underway (latency 65 ms) and were related to the displacement of the center of mass and active correction of trunk position. Shear forces showed both passive (inertial) and active components and suggested that the majority of the torque necessary for po,stural correction was generated by the hindlimb. EMG responses in forelimb and shoulder muscles were most correlated with increase in vertical force, showing a generalized co-contraction in tailward translation (when these limbs were loaded) and little activity when the forelimbs were unloaded. EMG responses in hindlimb showed reciprocal activation of agonists and antagonists during perturbation with strong synergies of thigh and foot flexors in tailward translation and thigh and foot extensors in headward translation. The forelimb EMG patterns were most consistent with the conclusion that the forelimb is used primarily for vertical support during perturbation. It was concluded that hindlimb EMG responses were appropriate for both vertical support and performance of the postural correction. The hindlimb muscle synergies observed during translation are the “mirror image” of those observed in humans by other workers.

Notes: Summary Between 4 and 10 weeks of age 10 normally reared kittens were bilaterally implanted with osmotic minipumps. The visual cortex of one hemisphere was infused with 4 mM 6-hydroxydopamine while the other hemisphere received only a vehicle solution. The pumps delivered the solutions at 1 μl/h for one week concurrent with monocular deprivation. Subsequent electrophysiological recording was performed blind and revealed a marked effect of the 6-OHDA treatment: while most cells in the control hemisphere were primarily activated by stimulation of the non-deprived eye, cells in the 6-OHDA-treated hemisphere were significantly more binocular. High pressure liquid chromatography revealed that the loss of normal ocular dominance plasticity in 6-OHDA-infused hemispheres was always accompanied by at least a 50% decrease in cortical norepinephrine levels and a smaller decrease in dopamine levels. Furthermore, there appeared to be a positive correlation of the degree of ocular dominance shift and the relative amount of norepinephrine present. These results are consistent with the hypothesis that catecholamines, especially norepinephrine, are normally required for ocular dominance plasticity during the critical period in kittens.

Notes: Summary Spatial summation was studied quantitatively through width response curves made with an optimally oriented test slit of variable width, and by comparing the response to combined presentation of several parallel slits with the response to each slit alone. Prior to summation analysis, the cell's discharge field (DF) was mapped by presenting a test slit ON and OFF across the receptive field. Activation profiles, showing the extension of subregions where light stimulation increased (enhancement) or decreased the firing rate (suppression), were made by presenting an optimally oriented activation slit in the most responsive DF-position. Against this activity the effects of a parallel test slit were determined in a series of broadside positions. Width response curves were made over the subregions of the DF and the activation profiles. Spatial summation was found in all cells, but the width of the summation region was smaller than the width of the subregions in the respective profiles. The width of the summation region was related to the degree of activation rather than to specific locations within the receptive field. The effect produced by several slits presented together deviated from the algebraic sum of the effects produced by each slit alone. Linear summation was rarely found. Accumulated response curves obtained by integration of DF or activation profiles were compared with width response curves to test linearity of summation. Linear summation throughout the whole receptive field was never found. A satisfactory fit was found only over a narrow region showing that summation was linear within a small part of the summation region. Linearity ended near response maxima or minima in the response profiles. The results indicate that the receptive field of simple cells consists of overlapping excitatory and inhibitory fields, and that the exact location and width of enhancement and suppression zones are determined by an activity-dependent balance between excitatory and inhibitory inputs.

Notes: Summary 1. The morphology of secondary vertical vestibular neurons was investigated by injection of horseradish peroxidase (HRP) into cells connected to the posterior canal system in rabbits (lateral-eyed animals) and cats (frontal-eyed animals). Vestibular neurons were identified by stimulation with bipolar electrodes implanted into the ampullae of the anterior and posterior (PC) semicircular canals of pigmented rabbits; in the cat, these cells were identified by natural and electrical stimulation. Axons monosynaptically activated by PC stimulation were injected with HRP in the medial longitudinal fasciculus (MLF). These were later reconstructed by light microscopy after the brains had been processed with a DAB-CoCl2 method. 2. In the rabbit the majority of the axons bifurcated after crossing the midline with one branch ascending and the other descending in the MLF. The ascending branches gave rise to collaterals that terminated in both the trochlear nucleus and the inferior rectus subdivision of the oculomotor nucleus. In addition some axons also sent collaterals into the paramedian pontine reticular formation, the periaqueductal grey and the interstitial nucleus of Cajal. The descending branches were followed to the caudal part of the medulla in the MLF and gave rise to collaterals terminating in the vestibular nuclei, the medullary reticular formation, the perihypoglossal nuclei, the abducens nucleus, and the facial nucleus. In another cell type axons crossed the midline without giving off any collaterals and proceeded caudally in the caudal MLF. The synaptic effects of the two types of cells were concluded to be excitatory and inhibitory, respectively. Cell bodies of contralaterally projecting neurons were located in either the medial or ventro-lateral vestibular nuclei. 3. In the cat we observed two neuron classes, with contralaterally projecting axons, whose synaptic effects are presumably excitatory. Their cell somata were located in the medial vestibular nucleus. Termination patterns were similar to both the trochlear and oculomotor nuclei, but neither projected to the abducens nucleus. One class of neurons was almost identical to that found in the rabbit with the main axon bifurcating in the MLF. The second type lacked a descending branch in the MLF. Axon collaterals of the latter type crossed the midline within the oculomotor nucleus after terminating in the inferior rectus subdivision to reach a similar portion of the ipsilateral oculomotor nucleus. Collaterals of these axons also terminated bilaterally in the supraoculomotor region between trochlear and oculomotor nucleus, the interstitial nucleus of Cajal and prerubral loci (including the fields of Forel). In similarity to the rabbit, presumed inhibitory vestibular neurons were found with axons directed caudally in the MLF without brain stem collaterals. 4. Ipsilateral neurons with ascending axons considered to be inhibitory were only studied in the rabbit. Their cell bodies were located in the superior vestibular nucleus, the axon joining the rostral MLF with major termination sites in the superior rectus and in the inferior oblique subdivisions of the oculomotor nucleus. Other terminations were in the paramedian pontine reticular formation and in the medullary reticular formation. 5. These data indicate strong similarities in the morphology of PC linked secondary vestibular neurons in the two species suggesting paramount importance for this wiring pattern in the spatial organization of eye movements. Variations in the termination patern likely reflect different kinematic characteristics of extraocular muscles necessary for the appropriate, but different, type of compensatory eye movements in lateral-versus frontal-eyed animals. We conclude that the termination pattern of secondary vestibular neurons forms a basic part of the neuronal matrix for space-time coordinated eye-movements and other related vestibular functions. This neuronal network provides a morphological basis for a conversion factor for the transformation of vestibular into e.g. extraocular muscle coordinates.

Notes: Summary Extracellular recordings have been made from 118 electrophysiologically identified neurones lying in the posterior lateral suprasylvian area (PLLS and PLMS) of cats anaesthetized with Nembutal. Eighty-one cells were activated synaptically by the electrical stimulation of cortical and subcortical sites known to be the sources of monosynaptic projections to the lateral suprasylvian area; latencies to such activations have been measured. The locations and sizes of the receptive fields of 55 neurones were determined. The direction sensitivity and ocularity of these cells also were examined. The effects of various pharmacological agonists and antagonists have been observed on visual responsiveness and synaptic excitability. The excitatory effects of subcortical (dorsal lateral geniculate nucleus and pulvinar nuclear complex) electrical stimulation on the activity of suprasylvian neurones were reduced substantially by the iontophoretic administration of atropine. Antagonists of the receptors for the excitatory amino acids reduced the effectiveness, on the single cell evoked activity, of stimulation of the ipsilateral 17/18 border region and contralateral homotopic lateral suprasylvian area. Both classes of antagonist reduced the magnitude of neuronal responses to photic stimulation, and these response attenuations were additive when the antagonists were ejected concurrently. All of the pharmacological effects were reversible and reproducible. These data lend support to the proposition that acetylcholine and an excitatory amino acid are mediators of synaptic transmission of cortical visual processes in the lateral suprasylvian area.

Notes: Summary The relations between the cerebral cortex and the red nucleus have been studied in acute, chloralose anaesthetized cats using intracellular recording techniques. Stimulation of the cerebral cortex induces in rubrospinal cells a short latency excitation followed by a long lasting silent period. The evidence is presented that at least a great part of the latter is due to genuine IPSP evoked in these cells. Three populations of rubrospinal neurones have been distinguished according to the cortical origin of their afferents: one group receives projections from the forelimb cortical area. These cells project to the cervical spinal cord and thus should control the forelimb. The second group receives projections from the hindlimb cortical area. These cells project to the lumbar spinal cord and should control the hindlimb. The third group of rubrospinal neurones receives convergent projections from both forelimb and hindlimb cortical areas. If these cells have collateralized axons terminating in both rostral and caudal spinal cord, they could contribute to the coordination of fore- and hindlimb movements. The projections originate in cytoarchitectonic areas 1–5 i.e. in the primary motor and sensory areas and in the rostral portion of the parietal area. No projection has been found from area 6 (premotor) or from area 7 (caudal parietal). The projection upon single rubrospinal cells has been found to originate from large cortical regions with a large overlap between those with excitatory and inhibitory actions. This could indicate the intermingling of cortical cells transmitting both effects.

Notes: Summary Using laminar field potential analysis, we examined responses elicited by both photic and optic nerve stimulations in 30 kittens of 0–65 days of age and in three adult cats. In adult cats, the response in the visual cortex on optic nerve stimulation is a wave complex which consists mainly of surface positive-depth negative (sP-dN) potentials. By contrast, the response in neonates consists of two surface negative — depth positive (sN-dP) waves. In 2 weeks, preceding the sN-dP waves, an sP-dN wave appears. As age increases, the sP-dN wave becomes of higher voltage and the sN-dP waves become of lower voltage. Thus, the configuration of the response resembles that of adult cats in 3–4 weeks. Both photic and optic nerve stimulations elicit responses of the same configuration in the same area. The extent of the responsive area is exactly the same at any age as in adult cats. Using the orthograde HRP method, we examined terminals of the geniculocortical afferent in 23 kittens of 0–43 days of age. The density of labeled terminals in layer I is much higher in kittens before 1 week of age (n = 8) than in kittens after 1 month of age (n = 5), whereas the density of labeled terminals in layer IV is higher in the older kittens than in the younger kittens. These electrophysiological and morphological changes are correlated in reference to the maturation of the neuronal circuit in the visual cortex.

Notes: Summary A series of simultaneous recordings from several striate cortex neurons were made in paralyzed, anesthetized cats. Recordings were obtained with one or two bundles of extra fine wires and originated from one and two cortical orientation columns. Standard PST histograms and, in some cases, response planes were used to analyse the neuronal receptive fields. Functional connectivity between neurons was assessed by cross-correlation of their spike trains. It was found that 61% of neuronal, pairs found within a column shared the same input, either excitatory or inhibitory. Even if neurons in a pair belonged to two different columns separated by 1 mm lateral distance, 40% of pairs still exhibited shared input coordination. This type of coordination could also encompass all combinations of simple and complex fields in the pair. Direct connections between neurons were found almost exclusively within columns: excitatory connections were found in 20% of cases and inhibitory in 8%. Direct connections were often accompanied by the other types of interactions. Only one example of excitatory and one of inhibitory direct connections were found between columns. In both cases preferred orientations were almost identical.

Notes: Summary The relative efficacy of distributed versus massed reverse occlusion therapy in promoting recovery from the anatomical and physiological effects of monocular deprivation was studied in two experiments performed on kittens raised with one eye occluded from eye-opening until 5 weeks of age. The first experiment explored the effects of different periods (ranging from 0.5 to 4 h) of reverse occlusion imposed daily for 20 days. The second, involving a fixed period of reverse occlusion (20 h), examined recovery with respect to the distribution of that period over a varied number of brief daily sessions. Recovery was assessed in terms of changes in cortical ocular dominance and lateral geniculate cell morphology. Although recovery of both cortical ocular dominance and geniculate cell morphology showed the same overall progression with increasing periods of reverse occlusion, changes were apparent in the lateral geniculate nucleus before changes were evident in cortical ocular dominance. A given period of reverse occlusion was found to be far more effective in promoting recovery when distributed over a number of different exposure sessions than when massed together in just one or two sessions. The data suggest that there is a maximal rate of cortical recovery which is achieved with surprisingly brief daily periods of forced visual exposure of the initially deprived eye.

Notes: Summary The subcortical projections to the lateral dorsal nucleus (LD) of the cat thalamus were studied with retrograde transport techniques. Deposits of horseradish peroxidase (HRP) or fluorescent tracers were placed unilaterally in LD of adult cats, using electrophoretic or pressure injection techniques. Following post-injection survival periods of 1, 2 or 3 days, HRP retrogradely labeled cells were identified in sections reacted with benzidine dihydrochloride; fluorescent labeled cells were identified by fluorescent microscopy. Injections in LD result in retrogradely labeled neurons in all nuclei of the pretectal complex, including the nucleus of the optic tract (NTO), the posterior pretectal nucleus (NPP), the anterior pretectal nucleus (NPA), the pretectal olivary nucleus (NOL), and the medial pretectal nucleus (NPM). Small electrophoretic injections of HRP were used to investigate a possible topographic organization of the pretectal projections. Results from a variety of injection sites indicate only a subtle rostral-caudal gradient. That is, small injection sites in rostral LD result in retrograde labeling of neuron somata in the rostral parts of NTO, NPA and NPP, and throughout NPM. Injections in caudal LD result in labeled cells more caudally situated in NTO, NPA, NPP, and throughout NPM. Injections in the pulvinar (Pul) also result in retrogradely labeled cells in the pretectal complex, particularly NTO, NPP, and NOL. Experiments with injections of distinguishable fluorescent tracers in LD and Pul reveal that many more cells project to Pul than to LD. These experiments also reveal that while neurons that project to LD are intermingled with neurons that project to Pul, the two projections originate from separate sub-populations of cells. These results are discussed in regard to phylogenetic comparison of pretectal projections and subcortical pathways of sensory input to the limbic system.

Notes: Summary Afferent input to the central cervical nucleus (CCN) in the C1–4 segments was studied with degeneration methods after sectioning of dorsal roots (DRs) or lesions in the spinal cord or brain stem. Degeneration in the CCN was heavy after sectioning of the DRs C1–4, moderate after sectioning DRs C5–8, and scanty after sectioning DRs T1–4. One to 2 days after sectioning of the C2 dorsal root the resulting degeneration had a granular appearance. At 4 days after the operation coarser argyrophilic fragments appeared, and this type of degeneration dominated at longer postoperative intervals. Degeneration in the ipsilateral CCN was found after lesions of the ventral and lateral funiculi of the thoracic cord. No degeneration was found after lesions of the dorsal funiculus caudal to T4 or after lesions in the ventral and lateral funiculi of the lumbar cord. Degeneration in the ipsilateral CCN was found after lesions in the brain stem in cases with lesions involving the medial and caudal part of the medulla. These afferents may run in the medial longitudinal fascicle (MLF).

Notes: Summary (1) Participation of the motor cortex in initiating muscle contraction in an isometric tracking task was assessed in cats trained to make accurate force adjustments using forelimb muscles, in response to a vibrissal/visual display stimulus. Behavior in the task was characterized by short reaction times. While the task was performed, recordings of single cortical units were made in zones within area 4γ defined by the effects of microstimulation in forelimb muscles and by receptive fields on the forelimb. (2) Two types of receptive fields with different regional distributions were observed. Cells with simple receptive fields (superficial or deep) were seen throughout the area sampled, consisting of the lateral half of the anterior and posterior sigmoid gyri. Cells whose receptive fields had complex features (directional specificity, temporal lability, multiple foci, etc.) were preferentially located in the cortex rostral to the cruciate sulcus. (3) The area of motor cortex rostral to the cruciate sulcus also differed from the area caudal to the cruciate sulcus in the timing of task-related activity. Neurons that were active before response onset (lead cells), and could therefore contribute to response initiation, were preferentially located in the rostral cortex, and, in general, had complex receptive fields. (4) Lead cells were active at a constant latency from the stimulus, rather than being timed to response onset. However, the modulation of their activity was related to both the direction and magnitude of the force response. (5) These results suggest that the pericruciate motor cortex of the cat contains two functional subdivisions: a caudal one concerned with ongoing movement, perhaps under the control of specific sensory inputs from the responding limb, and a rostral one involved in initiating movement. Because behaviorally relevant stimuli can rapidly activate a specialized population of cells in the rostral cortex, this area is able to participate in responses with short reaction times.

Notes: Summary The cells of origin and terminal distribution of the prefrontal corticotectal projection in the cat has been examined using retrograde cell-labeling with horseradish peroxidase (HRP) and anterograde axon-labeling with HRP or 3H-amino acid autoradiography. All prefrontal neurons labeled from unilateral enzyme deposits in the superior colliculus are pyramidal cells scattered through the thickness of layer V. The ipsilateral prefrontotectal neurons are located most densely in the banks and fundus of the presylvian sulcus and, to a lesser extent, in the anterior and frontal polar part of the gyrus proreus. About 10% as many cells are labeled in the contralateral prefrontal cortex in a similar distribution. Injections of HRP restricted to the superficial layers of the colliculus failed to label cells in the prefrontal cortex. Injections of HRP or 3H-proline-leucine in the region of these prefrontotectal neurons results in axonlabeling mainly, but not exclusively, in the ipsilateral superior colliculus where the labeled fibers are distributed in the layers below the stratum opticum. Labeled axons are especially dense in the intermediate gray layer where, caudally, they are arranged in two horizontally arrayed dorsal and ventral sheets interconnected by periodic columns of dense fiberlabeling interposed between columns of lesser fiberlabeling. Thus, the prefrontotectal projection of the cat here reported is consistent with that described earlier for the rat, but differs markedly from the primate in that prefrontal area 8 in monkeys projects also to the superficial tectal layers.

Notes: Summary Ocular movements of naive and adapted cats were recorded by classical electronystagmography techniques during: (1) sinusoidal vestibular stimulation, (2) sinusoidal optokinetic stimulation, (3) sinusoidal additive visual-vestibular stimulation, and (4) sinusoidal conflicting visual-vestibular stimulation. Adaptation of the horizontal vestibulo-ocular reflex (VOR) was produced in adult cats by sustained combined sinusoidal rotation of the cat and its surroundings (fixed-field conditions). This procedure was applied for four hours for four consecutive days. On the fifth day the VOR in darkness, the OKR, the VOR in the light and the visual suppression of the VOR were studied. VOR gain decreased from day to day and some relative frequency-specificity emerged. The gain of the visually inhibited VOR also diminished after training. This change was also frequency-specific. OKN gain, tested by a set of sinusoidal rotations, was found to be virtually unchanged. In the naive cat, VOR modified by the visual stimulus (fixed or moving) could be computed by an algebraic summation of the VOR and OKR eye movement compensations. After training, the gain of the VOR in situations where the VOR was interacting with the OKR remained easily predictable by the algebraic summation of the isolated VOR and OKR compensations.

Notes: Summary For the experiments reported in this study, recordings were obtained from 246 single units in the middle lateral suprasylvian visual area (LS) of 13 cats. 49 of these cells were subjected to detailed quantitative analysis. The receptive field (RF) organization was examined for directionally specific cells by presenting moving single spots on large moving random dot backgrounds. A cell's response to an optimal spot (in terms of size, direction, velocity) moving on a stationary background inside the excitatory RF (ERF) was compared to in-phase (same direction, same velocity) and anti-phase (opposite direction, same velocity) movement of spot and background. In-phase movement resulted in inhibition of the cell's response (3–100%) in 94% of the cells, while anti-phase movement led to reduced inhibition in 52% of the cells or to facilitation (0.5–327%) in 39% of the cells. By changing the direction of background motion with respect to that of the spot, the directional tuning of the in-phase inhibition and anti-phase facilitation effects was determined. We were able to manipulate the size of the background effects by masking out the background for various proportions of the ERF, and maximizing them by restricting background stimulation to the large inhibitory RF (IRF) surrounding the ERF. These results could be best accounted for by a double-opponent-process mechanism with both RF center and RF surround being directionally selective, but with opposite polarity. It is suggested that this type of mechanism could be involved in the processing of object motion.

Notes: Summary By means of retrograde axonal transport of fluorescent substances, e.g., Propidium Iodide, Fast Blue, and Nuclear Yellow, the present study was made to determine whether or not single neurons in the cat inferior colliculus share ascending and descending projections to the following two pairs of structures, i.e. (1) to the medial geniculate body and cochlear nuclei, and (2) to the superior colliculus and pontine nuclei. Our findings indicate that extremely few neurons, if any, in the inferior colliculus harbor such divergent axon collaterals, although most of the different types of projection neurons are located in the same subdivisions of the colliculus.

Notes: Summary (1)Pinna stimulation evoked rhythmic oscillations in the spinal cord of the decerebrate curarized cat (“fictitious” scratch reflex). The role of different spinal segments in generation of these oscillations was studied. For this purpose, destruction of the grey matter of one or of several spinal segments was performed. Besides, different numbers of caudal segments were disconnected from the rest of the cord by cooling the lateral surface of the cord. ENGs of muscle nerves and activity of spinal neurons were recorded. (2) Different parts of the lumbosacral spinal cord, i.e. the L3 and L4 segments disconnected from the caudal part of the cord as well as the isolated L5 segment, are capable of generating rhythmic oscillations with a frequency (3–4 Hz) typical of the scratch reflex. (3) Rhythmic activity of the more caudal segments (L6-S1) usually appears only provided the rostral segments (L3–L5) generate rhythmic oscillations. However, when the dorsal surface of the L6-S1 segments is cooled, pinna stimulation evokes rhythmic activity in these segments earlier than in the L3–L5 segments. (4) The hypothesis is advanced that the L3–L5 segments are the “leading” ones, i.e., they determine the rhythm of activity in the whole spinal hindlimb centre.

Notes: Abstract Inspection of eye saccades made by head-fixed, trained cats revealed the existence of many eye shifts at an approximately constant velocity during the deceleratory phase of the saccade or at the end of it. Slow eye movements occurring at the end of a saccade are usually referred to as “postsaccadic drifts”. It is shown that the duration and mean velocity of these “drifts” are related to the amplitude of the movement. The kinematics of these slow eye movements are nevertheless different from those of saccades. Slow movements at the end of the gaze shift have longer durations than those occurring during the intersaccadic interval between a saccade and a reacceleration of the eye. A closer study of the drifts of three trained cats showed that they play an important corrective role in reducing the residual error at the end of a saccade or during an intersaccadic interval. This functional corrective role was demonstrated by relating the amplitude of the slow movement to the amplitude of the residual error when the slow velocity eye shift began. It is therefore proposed to name these eye shifts “slow correcting movements”.

Notes: Abstract We measured rotation (horizontal, vertical and torsional) and translation (horizontal and vertical) of the paralysed cat's eye in response to 45° steps of orientation presented in a pseudorandom order around the roll and pitch axes (with respect to the horizontal canals). During changes of position of the animal in the roll plane, the eyes rotated towards the lowest part of the orbit (left with left ear down; top when the cat was upside down, etc.) by an average of 0.55°. Changing orientation in the pitch plane evoked vertical rotations of ±1.42° (upwards eye movement during forwards head pitch) and torsional rotations of ±1.3°. All these rotations taken together suggest that the centre of mass is in front of, below and temporal to the centre of rotation. The eyes translated temporally (thus separating by 0.72 mm) during forward pitching and there was a small vertical displacement (0.23 mm) when the animal was upside down. These findings are discussed with respect to a possible role of the extraocular proprioception system.

Notes: Abstract The cat hindlimb muscles have been classified, traditionally, as flexors and extensors, based on their actions in the parasagittal plane and their patterns of recruitment during locomotion and reflex responses. This study provides a detailed examination of the relative magnitudes of the various moment arms of the cat ankle muscles and the interdependent effects of position in the various axes of motion. We used a method based on observing small sliding movements of tendon in response to small angular displacements of the joint. Surprisingly, we found that the ankle joint of the cat permits substantial motion in three axes (eversion/inversion and abduction/ adduction as well as extension/flexion) and many muscles crossing the ankle joint have their largest moment arms about axes other than extension/flexion. These moment arms often depended on the joint position in the axis of the moment arm and, to a lesser degree, on the extension/ flexion angle as well. For some muscles (notably peroneus longus) there was sufficient variability that the predominant action in neutral posture (axis with the largest moment arm) could change from animal to animal, which may be related to heterogeneities of locomotor and reflex recruitment reported in the companion paper.

Notes: Abstract During stereotyped behaviors such as locomotion, patterns of muscle recruitment are usually quite consistent from animal to animal, even in the face of many surgical and pharmacological reductions. However, as studies of musculoskeletal structure, neuromuscular architecture, and sensorimotor circuitry become more detailed, it is important to ask whether there is some level of organization at which individual differences begin to dominate. This study concentrated on the small muscles of the foot and ankle, using standardized methods that consistently record stereotypical electromyographic activity from prime mover muscles and that permit wellcalibrated stimulation of cutaneous nerves to elicit reflexes during treadmill locomotion. Some muscles (particularly the main ankle extensors, triceps surae, and plantaris) had stereotyped activity during both unperturbed locomotion and reflex responses. Others had stereotyped activity during locomotion but variable reflex patterns among animals (tibialis anterior, extensor digitorum longus, flexor hallucis longus, and peroneus brevis). Still others had variable locomotor activity but reflexes that were consistent (flexor digitorum longus) or variable for only peroneal nerve stimulation (peroneus longus), only plantar nerve stimulation (peroneus tertius), or the two (flexor digitorum brevis). Among muscles with interanimal variability, there seemed to be no particular correlation between locomotor and reflexive recruitment in a given animal. This functional heterogeneity is discussed in terms of the development of locomotor and reflex programs and in the context of structural heterogeneity of some of these muscles that is described in the companion paper.

Notes: Summary Single cells were recorded extracellularly in the nucleus of the optic tract (NOT) in monocularly deprived cats. Monocular deprivation had no effect on the direction specificity of these neurons, i.e. all cells in the left nucleus preferred movements from right to left and all units in the right nucleus preferred movements from left to right in the visual field. Neurons driven from the deprived eye failed to respond to stimuli moving at velocities above 10°/s whereas neurons driven from the non-deprived eye responded to velocities up to and above 100°/s as do neurons in normal cats. In 8 out of the 10 cats tested all cells in the two nuclei could be influenced only from the contralateral eye irrespective whether this was the deprived or the non-deprived eye. In the other two cats the influence from the non-deprived eye on cells in the ipsilateral NOT was found to be normal. This influence is mediated probably via cortico-fugal projections. In the 8 abnormal cats a clear deprivation effect could be assigned for the first time to the non-deprived eye consisting in a loss of its connections to the ipsilateral NOT. Electrical stimulation of the visual cortex revealed, however, the existence of a connection between the visual cortex and the NOT. A possible explanation for the specific deficit with visual stimulation in the cortico-pretectal synapse ipsilateral to the non-deprived eye is discussed in relation to developmental mechanisms. The conduction velocity of retinal input to the NOT and the output of the NOT to the inferior olive remained uninfluenced by visual deprivation.

Notes: Summary Non-cerebellar afferents from visual relays to the vestibular nuclei (VN) of the cat have been re-evaluated with the use of the horseradish peroxidase technique. From our data it can be concluded that: (1) A monosynaptic projection from the nucleus reticularis tegmenti pontis to the VN can be excluded. (2) Monosynaptic projections from the superior colliculus and some of the pretectal nuclei (nucleus of the optic tract, olivary pretectal nucleus) to the nucleus prepositus hypoglossi may constitute polysynaptic visual afferents to the VN, which would account for the residual visual sensitivity of the VN neurons after cerebellar or inferior olivary lesions.

Notes: Summary This paper reports on experiments in which the effect of disconnexion of association fibres from Area 17/18 to the posterior suprasylvian cortex (PSSC) was investigated. In the control experiments, all neurons had large receptive fields in the central 5–10 ° of the visual field without detailled retinotopy. In the medial bank of PSSC, receptive fields were located in the contralateral visual field, while receptive fields of neurons in the lateral bank were located ipsilaterally. Neurons in PSSC could be excited by electrical stimulation of the ipsilateral Area 17/18 boundary, of the medial pulvinar (N. lat. post., pars, lat.) and the lateral geniculate body. About 2/3 of all neurons could be excited from all these regions, although with varying latencies. After acute and chronic subpial undercutting of the representation of the central 5–10 ° of the ipsilateral area 17/18, visual response properties including direction sensitivity, receptive field size and ocularity of PSSC-neurons in the medio-posterior bank did not change significantly. After ablation of the whole contralateral visual cortex (including PSSC and a wide region of the contralateral Clare-Bishop area) the input from the ipsilateral eye was considerably diminished, but other response properties did not change significantly. These essentially negative findings are discussed in relation to different findings of other authors, and it is argued that the subpial undercutting of only the central visual field representation may have prevented damage to the ipsilateral suprasylvian cortex and its afferents, which is difficult to avoid if the whole area 17 is ablated by suction. It is proposed, that association fibres may only “unspecifically” excite neurons in related association areas rather than impose onto them specific response features. These latter are derived, also in association areas, essentially from their thalamic afferents and their intracortical interaction.

Notes: Summary Small electrolytic lesions were made in the flocculus of two adult cats by means of a stereotactic approach avoiding any damage to the cerebellar nuclei. After a survival time of 3 days the animals were killed and the brains fixed and prepared according to standard procedures for ultrastructural studies. The brains of two unoperated cats were similarly treated and served as normal controls. In the experimental animals a large number of boutons in the rostral part of the nucleus prepositus hypoglossi (Ph) ipsilateral to the floccular lesion showed degenerative changes. These were characterized by hypertrophy, a prominent aggregation of densely packed parallel tubules or concentric arrays of cisternae and a filamentous hyperplasia. Only very rarely were such abnormal boutons seen in the caudal half of the ipsilateral Ph, or on the contralateral side or in the unoperated animals. The degenerating boutons contain clusters of pleomorphic vesicles and they establish symmetrical synaptic contacts with somata, dendritic shafts and dendritic spines. Some of the degenerating boutons appear to be of the en passant type. These findings thus affirm the existence of a direct flocculo-prepositus projection in the cat. It is suggested that this pathway could be responsible for mediating information about eye position and velocity to Ph neurons.

Notes: Summary The influence of horizontal optokinetic stimulation on posture and postural readjustments, induced by horizontal rotation of a turntable, were studied in the cat. Optokinetic stimulations at constant velocities lead to modifications of posture depending on the velocity of the stimulus. However, habituation as well as interindividual variability of these postural responses make difficult a systematic and quantitative approach to the phenomenon. Optokinetic stimulations at sinusoidal velocities induced reproductible postural responses, whose phase and gain were studied at different velocities and frequencies of stimulation. At low frequencies (from 0.05 Hz to 0.2 Hz) the postural responses tend to lead the position of the Optokinetic stimulus while a lag appears at higher frequencies (up to 1 Hz). In these conditions the gain increases and seems to depend on the performances of the simultaneously elicited oculomotor response. Induced postural readjustments are also modulated by the relative velocity of the visual stimulation with respect to the cat. A given visual input is more effective on an induced postural readjustment than on the posture of a static animal, especially at low frequencies (from 0.05 Hz to 0.3 Hz). These data extend to the cat the strong visual component of the postural control system previously described in other species.

Notes: Summary Cats were trained to discriminate temperature increases or decreases with the paws of one body half in a T-maze. The discriminatory proficiency was found to be inferior compared to cats who may use all four paws. The accomplishments of cats discriminating temperature decreases were superior to those of cats discriminating temperature increases. After transection of one lateral funiculus at the fifth cervical segment all of the cats lost the ability to discriminate temperatures with the contralateral paws. No thermosensory deficiency of the ipsilateral paws was observed. Five out of six cats recovered some ability to discriminate temperature differences with the contralateral paws, but no cat regained its preoperative proficiency within more than one and a half years postoperatively. The findings are taken to indicate the existence of more than one spinal, ascending, thermosensory pathway in the cat.

Notes: Abstract Stimulation of the mesencephalic reticular formation facilitates responses in the visual cortex elicited from the optic radiation. Using intraveneous administration of cholinergic antagonists we investigated in adult cats and two kittens whether this effect is mediated by cholinergic mechanisms. When administered alone the muscarinic antagonists atropine and scopolamine and the nicotinic antagonist mecamylamine failed to block reticular facilitation and sometimes even enhanced the effects of reticular stimulation. However, when administered in combination muscarinic and nicotinic antagonists eliminated or significantly reduced the facilitation. This was even true when the two antagonists were administered with a time lag of several hours. These results support the notion that reticular facilitation of cortical responses is mediated by cholinergic mechanisms and suggest that this effect is mediated either by a receptor with a mixed pharmacological property or by two independent pathways acting via nicotinic and muscarinic receptors. This hypothesis is discussed in the context of recent evidence on cholinergic transmission and earlier data on the pharmacology of reticular arousal.

Notes: Abstract Cholinergic afferents to the neocortex controlled by the mesencephalic reticular formation (MRF) are known to transiently facilitate cortical excitability. In an attempt to identify the pathway mediating this effect in the cat visual cortex we combined retrograde tracing techniques with immunocytochemical methods to visualize the acetylcholine-synthesizing enzyme choline acetyltransferase (ChAT). In addition we examined, in acute electrophysiological experiments, whether local neurotoxin injections into nuclei of the basal forebrain interfered with the reticular facilitation of cortical evoked potentials. Cholinergic projections to area 17 originate from different centers in the homolateral substantia innominata/internal capsule, the septal nuclei, and the nuclei of the diagonal band of Broca. No direct cholinergic projection from the MRF to the visual cortex was observed. Retrogradely labelled cells intermingled with ChAT-positive neurons in the brainstem generally revealed immunopositivity for catecholaminergic markers. Local injections of neurotoxins in the substantia innominata blocked reticular facilitation, whereas local lesions of the septal nuclei and the nuclei of the diagonal band had no effect on MRF-induced facilitation. The blockage of the reticular facilitation of cortical evoked responses after unilateral lesions of the substantia innominata was bilateral, suggesting a cooperative interaction between basal forebrain structures of the two hemispheres. The anatomical and physiological data are discussed with respect to possible mechanisms of transient brainstem influences on cortical excitability.

Notes: Summary The climbing fibre pathway from the tectum to posterior cerebellar cortex was investigated in chloralose anaesthetized cats. With low threshold electrical stimulation within the deeper layers of the superior colliculus, climbing fibre responses were recorded in a centrally located, longitudinal area of lobulus VII, oriented perpendicular to the long axis of the folia. This same area showed climbing fibre evoked activity regardless of the side of tectum stimulated. Hence, it was concluded that the tectoolivocerebellar pathway terminates bilaterally in the most medial parts of the cerebellar cortex, the termination zones being denoted the a1 zones. The results were discussed in relationship to recent anatomical knowledge of the tecto-olivary projection and of the olivocerebellar projection to lobulus VII, and indicate that descending paths from the brain stem to the inferior olive might “respect” its intrinsic compartmentalization.

Notes: Summary Recordings were made of isometric contractions of single motor units of the cat's m. peroneus longus (PerL). The units were activated by stimulation of dissected filaments of ventral roots. In accordance with the general principles introduced by Burke et al. (1973), the 80 isolated PerL units were classified into three or four type-categories according to their contractile speed and endurance. Three currently used varieties of a “fatigue index” were calculated and found to give equivalent results. Units with a high, intermediate and low resistance to fatigue were responsible for about 22.5, 25.4 and 52.1% respectively of the total muscle force. Two alternative methods for fast/slow categorization were compared: (i) classifying all units as slow that failed to show a “sag” in partly fused contractions (“sagcriterion”, Burke et al. 1973) and (ii) classifying all units as slow that had a more prolonged twitch contraction time than that of fatigue-sensitive units (‘FF vs. S-criterion’). The relative contribution of slow units to total muscle force was about 2.8 times as great (14 versus 5%) for a classification by the FF vs. S-criterion than for a subdivision according to sagging behaviour. When compared to equivalent data from previously published studies of feline hindlimb muscles, peroneus longus was found to resemble gastrocnemius medialis in relative motor unit composition. The maximum force of individual PerL units was, however, on average ≤ 50% of that reported for corresponding types of gastrocnemius units.

Notes: Summary The effect of intravenous infusion of dopamine (10 and 25 μg·kg−1·min−1 consecutively) on visceral blood flow distribution was examined in anesthetized cats using the microsphere technique and electromagnetic flowmetry. Arterial blood pressure did not change in response to dopamine infusion, but blood flow through the superior mesenteric artery, and blood flow in the mucosa-submucosa of the gastric antrum and various gut segments increased significantly. During infusion of the high dose the increase was most marked in the mucosa-submucosa of the antrum (+355%) and distal colon (+371%). By contrast, blood flow decreased in the muscularis-serosa of the gut segments investigated, in the spleen, pancreas, and the hepatic arterial bed. The increase in blood flow through the superior mesenteric artery was blocked by the dopamine antagonist bulbocapnine (10 mg/kg i.v.). The results suggest that the receptors mediating the dopamine-induced vasodilation in the gastrointestinal tract are located in the resistance vessels of the mucosa-submucosa.

Notes: Abstract Afferent fibres, in the inferior splanchnic nerves and lumbar white rami, which supply the colon and its mesentery in the cat, were investigated for their responses to distension and contraction of the colon and to local pressure applied to colon and its mesentery. 1) 63% (177 out of 287) of the axons had resting activity (median 0.3 imp/s). These axons were either unmyelinated (conduction velocity below 2 m/s) or thin myelinated (conduction velocity below 18 m/s). Most axons without resting activity (N=95 out of 106 axons) conducted at less than 1.4 m/s, and most were probably sympathetic efferents. 2) 76 out of 80 afferent units with resting activity (95%) and 8 out of 27 units without (30%) were excited by distension of the colon. The thresholds were largely at intraluminal pressures of around 25 mm Hg or higher. 3) Most afferent units (87%) responded with an increased steady state discharge throughout the distension with or without initial dynamic response. The rest of the afferent units responded only with a transient discharged to distension. 4) Most afferent units reacted in a graded manner to variable intraluminal pressures. 5) In only 43% of the distension-sensitive afferent units could mechanoreceptive sites be located on the wall of the colon or in the mesentery. The majority of the afferent units had one mechanoreceptive site only, some had two. 6) Afferent units reacting to colon distension were also excited by contraction of the colon. 7) The excitability spectrum of visceral afferent fibres in the inferior splanchnic nerves, which are activated by colon distension, suggests that these units are involved in visceral nociception from the colon.

Notes: Abstract Postganglionic sympathetic neurones supplying skeletal muscle and skin can be activated from the preganglionic site via cholinergic nicotinic, muscarinic and non-cholinergic synaptic mechanisms. The experiments described in this paper were designed in order to show that postganglionic vasoconstrictor neurones supplying skeletal muscle can be activated by the naturally occurring discharge pattern in preganglionicaxons when the nicotinic transmission is blocked. For this purpose, the activity was recorded simultaneously from postganglionic vasoconstrictor axons supplying skeletal muscle and vasoconstrictor axons supplying hairy skin. The preganglionic neurones were driven reflexly by stimulation of the arterial chemoreceptors. 1) During blockade of nicotinic transmission muscle vasoconstrictor neurones were activated via the CNS during stimulation of arterial chemoreceptors. This activation is either generated by muscarinic action of released acetylcholine or by a noncholinergic synaptic mechanism. 2) Postganglionic cutaneous vasoconstrictor neurones were inhibited during stimulation of arterial chemoreceptors. During blockade of cholinergic nicotinic transmission these neurones were not activated reflexly by stimulation of arterial chemoreceptors although they received inputs via cholinergic muscarinic and noncholinergic synaptic mechanisms. 3) The results illustrate that postganglionic vasoconstrictor neurones supplying skeletal muscle can not only be activated via non-nicotinic synaptic mechanisms through synchronous repetitive electrical stimulation of preganglionic axons but also by the discharge pattern produced in preganglionic neurones during stimulation of arterial chemoreceptors.

Notes: Abstract With quantitative techniques at electron microscopical level chromatin condensation and emptying of the interchromatin space have been established in the nuclei of the endothelial cells of small uterine vessels. The nuclear and cytoplasmic changes after cadmium administration show much similarity between endothelial cells of small uterine vessels and cultured liver parenchymal cells. Cytoplasmic changes in both cell types after cadmium administration are suggestive of a disturbance in ribosomal RNA synthesis as the main cause leading to ultimate cell lysis.

Notes: Abstract Male Wistar rats received methyl methacrylate monomer (MMA) i.p. in olive oil 1.0 g/kg body weight on 3 successive days. The weight of the livers and kidneys, and the body weights did not differ from their controls. On the fifth day after treatment, hepatic NADPH-cytochrome c reductase, 7-ethoxycoumarin 0-deethylase and the 2,5-diphenyloxazole hydroxylase exhibited maximal decreases in activity (25%, 58%, 36%, respectively) without any coincident effect on the total amount of cytochrome P-450 hemoprotein itself. One week later these activities had returned to control levels. The enzymatic changes in the kidneys were smaller in magnitude, and they were also reversed sooner. A single i.p. dose of MMA (2 g/kg body weight) caused elevation of serum alanine aminotransferase activity. A tenfold increase of the excretion rate of urinary thioethers was also discovered. The hepatic reduced glutathione (GSH) was depleted in 3 h to 20% and the GSSG to half of the value in controls. In kidneys, the GSH was decreased to 48% in 3 h before an apparent phase of overrecovery. At the end of the 24 h observation period, cytochrome P-450 concentrations were somewhat decreased in the liver. The GSH contents showed dose and time-dependent reversible decreases in isolated hepatocytes when incubated for 2 h in a medium containing MMA at the nominal concentrations of 0,2,5, or 10 mM. None of the treatments affected either the content of cytochrome P-450 or the viability of the liver cells.

Notes: Abstract In rodents fenofibrate shares with other triglyceride-lowering agents the potential to increase the liver peroxisome population. It was therefore of interest to look for this effect in hyperlipoproteinemic patients receiving this drug. Light and electron microscopy of liver biopsies from a group of 10 patients treated with fenofibrate and from another group of 15 receiving diet only, show no morphological difference between both groups. In contrast with the rodent data the morphometric study reveals no significant changes in the number (fenofibrate group: 7.96 1010 cm−3; group receiving diet alone: 8.41 1010 peroxisomes/cm3 of liver tissue) or in the size (fenofibrate group: Diameter=0.53±0.07 μm — group receiving diet alone: 0.50±0.06) of peroxisomes. The difference between our results and those obtained consistently in rodents may be due to the relatively low dose in man and/or a species-dependant difference in enzyme content of liver peroxisomes, itself related to an apparent difference in the way in which lipids are handled.

Notes: Abstract Interaction of zinc with mercuric chloride and sodium selenite was studied in the rat at the organ and subcellular levels (liver and kidneys). Zinc chloride was administered subcutaneously at dose of 5 mg Zn/kg, mercury chloride into the tail vein at a dose of 0.5 mg Hg/kg (both metals every other day during 2 weeks) and sodium selenite intragastrically, at doses of 0.1 mg Se/kg, every day. Zinc retention in the rat did not exceed 20% and was unchanged in the presence of mercury. An interaction effect was reflected by an increased whole-body retention of zinc by selenium, mercury, and selenium. In the presence of selenium no peak of metallothionein-like proteins stimulated by zinc or mercury was found in the soluble fraction of the kidneys. The metallothionein level did not differ from that typical for control group animals, too. A significant increase in the level of endogenous copper was found only in the kidneys of rats exposed to zinc in the presence of mercury and selenium.

Notes: Abstract The renal distribution of 125I-labelled metallothionein (125I-MT), administered as a tracer dose to female Wistar rats, has been investigated by light and electron microscopical autoradiography. 125I-MT was absorbed rapidly and 80% of the administered dose was observed in the kidney within 60 min after dosing. At 30 min, a high density of silver grains due to 125I, was observed by light microscopy in the convoluted proximal tubules. Electron microscopical autoradiography showed that silver grains were located in large apical vacuoles and cytoplasmic bodies (heterolysosomes) of the endocytotic system in the apical or middle regions of the cells lining convoluted proximal tubules. The results suggest that endocytotic systems are associated with 125I-MT absorption by epithelial cells lining the renal convoluted proximal tubules. The apparent inconsistency on the distribution pattern of silver grains due to 109Cd-labelled MT and 125I-labelled MT in these is also discussed.

Notes: Abstract The renal handling of humanβ 2-microglobulin (β 2-m) was investigated in normal rat and in rat with cadmium-induced renal damage. Cadmium was administered either in drinking water at a concentration of 100 ppm for up to 16 months or by i. p. injection of 1 mg Cd/kg, five times a week for up to 4 months. When renal dysfunction has developed, namely after 2 and 10 months of the i. p. and oral treatment respectively, unlabelled humanβ 2-m was injected intravenously and its disappearance in serum and its urinary excretion were studied by means of a sensitive immunoassay. In serum, the level ofβ 2-m drops by about 90% during the 10 first min, then declines more slowly with a half life around 20 min. Serum disappearance curves ofβ 2-m in normal and cadmium-treated rats did not differ markedly. The amount ofβ 2-m recovered in urine during the 4 h following the injection averaged 0.03% of the injected dose in normal rats. It increased on the average to 10% in rats treated i. p. with 1 mg Cd/kg for 3 months. However, in rats given 100 ppm Cd per os for 10 months, this amount averaged only 0.14%. A similar value was observed 5 months later, although at that stage, the critical level of cadmium in kidney cortex had been reached for 6–7 months. These data which were in accordance with the disturbances of the other renal parameters measured in cadmium-treated rats indicate that: 1) humanβ 2-m is reabsorbed by rat kidney at a similar rate as by human kidney; 2) if the occurrence of cadmium tubulopathy is concomitant with the saturation of cadmium-binding sites in kidney, its severity depends greatly on the rate at which cadmium reaches the saturated kidneys.

Notes: Summary The mitochondrial (mt) DNA of the aquatic phycomycete Allomyces macrogynus is a circular molecule with a size of 56.1 kbp. The cleavage sites for the restriction enzymes SalI and PvuI were mapped by comparing the partial denaturation patterns of isolated restriction fragments with the pattern of the intact circle. The genes coding for the small and large ribosomal RNA (rRNA) were located on the restriction map by heteroduplex and R-loop analysis. The gene coding for the large rRNA contains an intervening sequence, app. 0.7 kbp in size, near the 3′-end of the gene. The two rRNA genes are encoded on the same strand of the mtDNA and separated by a region of 17–18 kbp. This rRNA gene organization is similar to that found with members of the Ascomycetes.

Notes: Summary The morphology and chronology of an absolute ischemia was investigated on the small intestine of man and rat. It could be shown that the morphogenesis of ischemic damage to the intestinal mucosa in man does not differ from that in the rat. However, there are crucial and in therapeutic terms significant differences in the time course of the ischemic damage to the intestinal mucosa. Whereas in the small intestine of the rat, the first appreciable alterations — detachment and disruption of the lining epithelium at the villous tip — are already to be observed after absolute ischemia lasting 15 min, in the human small intestine the same lesions only occur after 4 h. A comparable complete necrosis of the small intestinal mucosa was detected in the rat after 7-h ischemia, and in man after 44-h ischemia.

Notes: Abstract The photosynthetic membranes of the five bchl b-containing bacteria Ectothiorhodospira halochloris, E. abdelmalekii, Rhodopseudomonas viridis, R. sulfoviridis and Thiocapsa pfennigii have been investigated by electron microscopy and digital image analysis. All five species have the photosynthetic complexes hexagonally arrayed in the membrane with lattice spacings close to 13 nm, except for R. sulfoviridis and T. pfennigii which display somewhat smaller (∼12.5 nm) lattice spacings. Correlation averaging which imposes less stringent requirements on the lattice perfection than conventional Fourier filtration techniques has been employed to elucidate the structure of the photosynthetic complexes. Their basic organization, i.e. a ring, probably containing the light-harvesting (LH) polypeptides, surrounding a core (the “reaction centre”) appears to be almost identical for all species under scrutiny. Despite a resolution of ∼1.6 nm, however, little further significant substructure can be deduced from the averages; possible reasons for the “blurred” appearance of the LH-ring and absence of any subdivision in the reaction centre are discussed along with strategies aimed at obtaining a more detailed model of the molecular architecture of the photosynthetic membranes.

Notes: Abstract Due to the lack of an emergent flagellum the green flagellate Euglena mutabilis is restricted to gliding motility. During forward movement, the organisms orient positive phototactically in the presence of a suitable light stimulus. The cell contains both a stigma and a paraflagellar body which differ in shape and size from the organelles found in E. gracilis. The degree of orientation in white light follows an optimum curve with a maximum at about 100 lx. The spectral sensitivity shows a number of prominent peaks in the blue and green regions and extends well into the red region of the visible spectrum. Since the cell does not rotate during locomotion a periodic shading mechanism cannot account for phototactic orientation. Thus, phototaxis in the related species, E. gracilis and E. mutabilis differ in their photoreceptor molecules, their sensory transduction chains and their strategies of light direction detection.

Notes: Summary The “borderline lesion” of the stomach (severe dysplasia of the protruded type) is nowadays considered to be a true precancerous lesion. Histologically, this lesion is characterized by a proliferation in the area of the glandular neck, combined with severe cellular atypia. Investigation by means of transmission electron microscopy reveals the structure of these cells to be very similar to the structure of cells of an intestinal-cell-type carcinoma of the stomach. In addition to signs for a loss of differentiation of the cells, such as the absence of rough-surfaced endoplasmatic reticulum, mucin granules, and of the polarity of the cells, remarkably frequently luminal bulges and “blebs” developed to various extents can be detected. Morphometric analysis is delineating the tendency of structural features of the borderline lesion to develop toward the gastric cancer cell. These irregularities might be expressions of the beginning of expansive growth and signs pointing to differentiation into malignant neoplasia.

Notes: Abstract Single sections of superficial proximal convolutions of rat kidney were microperfused in vivo and in situ. The perfusion fluids contained radioactively labelledl- ord-aspartate,l-glutamate,l-pyroglutamate, or N-methyl-d-aspartate.l-γ-Carboxyglutamate as well as the other amino acids were added in the unlabelled from. Results.l- andd-Aspartate (0.073 mmol·1−1) are quickly resorbed at about the same rate.d-Aspartate resorption was blocked byl-aspartate (5 mmol·1−1) but not by β-alanine (5 mmol·1−1).l-Aspartate resorption was inhibited byl-glutamate (2 mmol·1−1) but not byd-glutamate,l-asparagine,l-phenylalanine or by succinate (2 mmol·1−1, each). The fast resorption ofl-glutamate (0.073 mmol·1−1) was blocked byd-aspartate,l-cysteate (2 mmol·1−1), but not by 3-mercaptopicolinic acid (0.15 mmol·1−1),l-glutamine, 2-oxoglutarate, taurine, N-methyl-l-glutamate or kainic acid (2 mmol·1−1, each).l-γ-Carboxyglutamate (0.66 mmol·1−1) and N-methyl-d-aspartate (2μmol·1−1) were found to be resorbed only at an extremely small rate.l-pyroglutamate (0.076 mmol·1−1) resorption was not influenced byl-glutamate (1 mmol·1−1). Fractional excretion of γ-carboxyglutamate was 7–25% (l-from) or 45–70% (d-form) at an artificially elevated plasma level of 12μmol·1−1. It is concluded thatl- andd-aspartate,l-glutamate,l-cysteate and, to a much smaller extent,l-γ-carboxyglutamate, are accepted by the tubular resorption mechanism highly specific for “acidic” amino acids. N-Substitution, the amidation of the β- or γ-carboxyl group, or the removal of the α-amino moiety almost completely abolish the ability of such compounds to be resorbed via this carrier; N-methylated or γ-carboxylated derivatives of “acidic” amino acids are not resorbed at all from the proximal tubule. The resorption of glutamate, but not of aspartate, is highly stereospecific.

Notes: Summary The effects of supramaximal vagus nerve stimulation on heart rate were studied in newborn rabbits, cats and guinea pigs. The analysis of the stimulus-effect curve revealed that the carlier proposed relationship: logI f/I o=H·f (I o is the steady state PP-interval before andI f during stimulation,f is the stimulus frequency, andH the slope of the line) accurately summarizes the relation in rabbits, while with minor deviations it also holds for newborn cats and guinea pigs. Thus, the vagus effect for each nerve and animal is characterized by the slope of the line,H. In rabbits and cats the vagus effect decreased during the first postnatal week to about 1/3 and 1/5 of the initial value at birth. Guinea pigs, however, did not show such a postnatal change of the vagus effect. In comparison with rabbits and cats these animals are born at a relatively late ontogenetic stage. Therefore, we hypothesized that the decrease in vagus effect is related to the stage of development and occurs mainly before birth in this species.

Notes: Abstract A differential equation model of the renal countercurrent system has been developed and physiological data from nephron segments were incorporated together with recently suggested urea recycling from renal pelvis to inner medulla and, particularly, an exponential reduction in the number of collecting tubules towards the renal papilla. The role of these features for the countercurrent concentrating mechanism has been studied by simulation runs. The computations, using the multiple shooting method, provide predictions about concentration profiles for salt and urea in tubes (nephron segments) and in the central core along the entire medullary countercurrent system. The results indicate that this model, without active salt or urea transport in the inner medulla, yields concentration gradients along the medullary axis compatible with those measured in the tissue.

Notes: Summary The direct histochemical detection of β-blocker binding sites was studied in sections of rat kidney using an immunohistochemical technique developed in our laboratory. Frozen sections of rat kidney were incubated in a solution of (-)alprenolol, washed, exposed to fluorescent (-)alprenolol antibodies (FAA) and then observed at a fluorescence microscope. Strong fluorescence was found within the wall of renal artery and vein, but primarly in the artery. At the level of blood vessels(-)alprenolol binding sites were located chiefly in the media and in the intima. The renal glomerulus, the loop of Henle and collecting tubules appear to be free of any fluorescence. Consequently they do not have β-adrenoceptors. On the contrary, the glomerular afferent and afferent arterioles, the cellular elements of the juxtaglomerular apparatus, proximal and distal convoluted tubules, are rich in (-)alprenolol binding sites. At higher magnifications the immunoreactivity appears to be located in the basal membrane of cellular elements which indicates that (-)alprenolol binding sites are membrane receptors. The direct immunohistochemical detection of β-blocker binding sites in the kidney may offer useful information concerning the site of action of β-blockers at the level of an important target organ for this class of drugs.

Notes: Summary The posterior hypothalamus of anaesthetized cats was superfused with artificial CSF through a push-pull cannula and the arterial blood pressure was recorded in the femoral artery. The release of endogenous histamine was determined in the hypothalamic superfusate by a radioenzymatic assay. Intravenous injection of sodium nitroprusside elicited a fall of blood pressure which was accompanied by an increase in the rate of release of endogenous histamine in the posterior hypothalamus. Similary, a controlled bleeding lowered the arterial blood pressure and enhanced the release of histamine. The durations of depressor responses to nitroprusside or controlled bleeding coincided with the duration of the changes in the rate of release of histamine. Intravenous injection of chlorisondamine also lowered the arterial blood pressure and augmented the release of histamine. However, the hypotension lasted longer than the increased release of histamine in the hypothalamus. Intravenous injection of noradrenaline elicited a rise in the arterial blood pressure which was associated with an increase in the release of histamine in the posterior hypothalamus. Intravenous injection of tramazoline led to a long-lasting hypertension and to a short-lasting increase in the release of histamine. Transection of the spinal cord at C1/C2 elicited a pressor response which was followed by hypotension. Increase and decrease in the arterial blood pressure were associated with an increased rate of release of endogenous histamine. A second transection of the spinal cord at a higher level did not influence either blood pressure or rate of release of histamine. It is concluded that increases and decreases in the arterial blood pressure enhance the rate of release of endogenous histamine in the posterior hypothalamus of the anaesthetized cat. The alterations in the release of histamine seem to represent an immediate response of the hypothalamus to changes in peripheral blood pressure.

Notes: Summary Bladder vessel walls of 20 patients with interstitial cystitis were studied by the electron microscope. 14 (70%) had severe endothelial injury. 10 (50%) showed injured smooth muscle cells. Odd basement membrane proliferations and disruptions were seen. Clusters of microfibrils about 10 nm in diameter and numerous partially membrane-bound vesicles of 100–600 nm with granular or tiny vesicular content (“granulovesicular bodies”) were also seen. Intercellular junctions of endothelial cells were open and there was emigration of polymorphonuclear leucocytes and platelets. The findings show pronounced vascular injury to have taken place, with neoformation of elastic tissue. It is suggested that the injury is immunologically mediated and that particularly those clusters of connective tissue microfibrils not yet covered by an amorphous elastin component may be involved in the pathogenesis of this disease.

Notes: Summary A clinico-pathological, light microscopic and immunohistochemical study of 15 clear-cell sarcomas, with an ultrastructural analysis of 6 of the tumors, is presented. The tumors showed a strong predilection for tendons and aponeuroses of the extremities in predominantly young and middle-aged people. The clinical setting, course and light microscopic appearance agree well with the original description by Enzinger (1965). Nine of the 15 patients developed metastases, most of them including lymph nodes, and 8 of the patients had died at the time of follow-up (median follow-up time 4.8 years). Reducing pigment was demonstrated within the cells of 2 tumors. Ultrastructurally the 6 tumors studied had a uniform appearance with characteristically rounded or oval tumor cells with a single nucleus containing one or two very prominent nucleoli, a light-staining cytoplasm with a moderate amount of organelles and a variable content of glycogen. Polymorphic melanosomes were seen in the cells of one of the tumors. External laminas enclosed groups of tumor cells and invested parts of individual tumor cells. With immunoperoxidase analysis for S-100 protein positive staining was observed in the vast majority of the tumor cells of all 15 clear-cell sarcomas. Metastases appearing in 9 of the 15 cases showed positive staining for S-100 protein. There was a strong staining of the cytoplasm and generally a weak and varying staining of nuclei. The immunohistochemical and electron microscopic findings indicate that clear-cell sarcoma is a homogenous entity among soft tissue sarcomas, of probable neural crest derivation.

Notes: Summary Bone marrow from hematologically healthy adults was exposed to a number of fixation procedures for investigation of the heterogeneity of the granule population in neutrophil granulocytes at the ultrastructural level. Four main cell stages were distinguished: early promyelocyte, late promyelocyte, myelocyte, and mature neutrophil granulocyte and described separately; metamyelocytes and band-form or stab cells are described together. The characteristic changes in the cytoplasm during myelopoiesis were analysed quantitatively. Special attention was given to the development of the granule population. Three types of granule arise in successive cell stages: granules which develop a sub-structure in the matrix (nucleated granules) are formed in early promyelocytes, granules with a homogeneous electron-dense matrix (azurophil granules) in late promyelocytes, and granules with a less electron-dense matrix (specific granules) in myelocytes. The three types of granule remain present during myelopoiesis. The best results in distinguishing the granule types were obtained by prefixation either in 0.1% glutaraldehyde or in 1.5% glutaraldehyde followed by washing in phosphate-buffered Ringer solution to which aminotriazole had been added. Granule counts revealed for the mature neutrophil a total number of granules of about 220 per ultrathin section. This population of granules is composed of about 12% nucleated, 11% azurophil, and 77% specific granules. When our previous findings are taken into account, the existence of three successively formed and morphologically distinguishable types of granule in heterophil (neutrophil) granulocytes has been demonstrated for three mammalian species: the guinea pig, the rat, and man. A separate term for the early promyelocyte stage is proposed: eomyelocyte.

Notes: Summary Lumps of electron-dense material were observed in synaptic clefts associated with all types of photoreceptors, in the vicinity of the synaptic ribbons, in the retinae of dark-adapted frogs. Frogs were reared under a cyclic illumination (light on at 8:00; light off at 20:00) and then exposed to one of two courses of dark adaptation: one started from 11:00 in the morning, and the other started from 20:00 in the evening. The synaptic clefts of red rods became wider at some places where spherical or polygonal lumps of dense material were accumulated. The frequency and sectional area of the lumps increased faster for the first hour in the regime starting from 20:00 than in the regime starting from 11:00, then they reached the similar saturation levels of about 0.6 (per ribbon) and 1.6 to 1.8×104 (nm2) in both the regimes. In greenrod synapses, plate-shaped lumps of dense material were present in synaptic clefts and interspaces between the processes of second-order neurons. In cone synapses at the end of about 1 h darkness, the frequency and area of the lumps reached maximum values of about 0.12 (per ribbon) and 9×103 (nm2) in the regime starting from 11:00 and, about 0.08 (per ribbon) and 4 × 103 (nm2) in the regime starting from 20:00. On exposure to light, the dense material abruptly disappeared from all types of photoreceptor synaptic clefts. Large dense-core vesicles, occasionally observed in light-adapted rod photoreceptor terminals, seem to participate in exocytosis of the dense material. The number of dense-core vesicles per synaptic ribbon in a terminal was about 0.55 at the end of 3 h light in the morning and about 1.28 at the end of 12 h light in the evening. The increased number of dense-core vesicles during the daytime may contribute to the faster accumulation of dense material in the synaptic clefts. Although the chemical identification or the functional significance of the electron-dense material remains unknown, it is interesting that this material showed a rise and fall in response to darkness and illumination. Also the fact that this material is clearly visible will be helpful for future analysis of frog photoreceptor synapses.

Notes: Summary A double plasma membrane (DPM) surrounding intestinal microvilli of the migratory milkweed bug, Oncopeltus fasciatus, is described. Mutant and wild types of the phytophagous insect have been studied by conventional SEM and TEM procedures with the use of membrane-enhancing staining methods. Longitudinal and transverse sections revealed a DPM surrounding microvilli and continuing over the apical portions of the intestinal cell. The outer membrane of the DPM contributes to an intestinal lining or peritrophic membrane (PTM), which apparently accumulates in layers. SEM studies reveal a rugose intestinal surface and complete PTM in both starved and fed insects. Only rarely are exposed microvilli seen by SEM. SEM examinations also enable the observation of numerous blebs on the luminal side of the PTM apparently held in position by a neck-like attachment and apparently derived from the outer membrane of the DPM. Preliminary TEM studies of microvilli revealed unique microvesicle-like structures, lying just inside the inner membrane of the DPM, which may be of membrane origin based on their typical trilaminar appearance after en bloc staining with uranyl acetate. Highly ordered microfilaments were observed to occupy the most central aspect of the microvilli.

Notes: Summary The renin substrate, angiotensinogen, was localized by immunocytochemistry in liver and kidney of normal rats by the use of an antiserum directed against pure rat angiotensinogen. This substrate was also examined in rats after bilateral nephrectomy, which is known to increase plasma angiotensinogen, and in rats treated with colchicine, which inhibits serum protein secretion. In normal rat liver, light microscopy showed the presence of immunoreactive material in a very few cells. The number of stained hepatocytes rose in rats treated with colchicine or after bilateral nephrectomy. Immuno-staining increased further when rats were both nephrectomized and colchicine treated. In the kidney, angiotensinogen was specifically located as granular formations in nephrocytes of the proximal tubule but never in the granular cells of the juxtaglomerular apparatus. The localization of these granular formations under the brush border suggests that angiotensinogen is reabsorbed from the glomerular ultrafiltrate rather than synthesized in the kidney.

Notes: Summary Substance P-like immunoreactivity (SPLI) was studied by immunocytochemistry and radioimmunoassay in the cerebral arteries, choroid plexus and dura mater of the guinea-pig, rabbit, cat and man. The highest concentrations were found in cerebral blood vessels: 6.1±2.3 pmol/g (guinea-pig), 9.0±1.1 pmol/g (rabbit), 7.1±0.4 pmol/g (cat), and 2.4±0.9 pmol/g (man). Lower levels were obtained in the choroid plexus and dura mater. The distribution of substance P (SP)-immunoreactive nerve fibres found in various regions of the guinea-pig correlated well with the amount of SPLI measured. Sympathectomy did not alter the concentration of SPLI in the dura mater or in cerebral blood vessels. Electrical field stimulation or 124 mM potassium enhanced the spontaneous efflux of SPLI by 10 and 20%, respectively, from superfused pial arteries in vitro. These data are in support of a functional role of perivascular SP within the cranial circulation.

Notes: Summary Vasopressin-containing neurons, identified by immunocytochemistry, are located predominantly in the posterior magnocellular division of the paraventricular nucleus of the rat hypothalamus. By electron microscopy, the immunoreaction product is seen within the cell bodies and neuronal processes. In the perikarya and dendritic processes, the immunoreactive material is associated primarily with neurosecretory granules. Axonal processes, identified by their content of microtubules and accumulation of neurosecretory granules, show the immunoreaction product in association with both of these organelles. Afferent axo-dendritic, axo-somatic and putative axo-axonic synapses with immunostained vasopressinergic neurons can be identified. The presynaptic profiles do not contain immunoreactive material. This study contributes to the ultrastructural characterization of vasopressinergic neurons in the paraventricular nucleus and of their afferent synaptic input.

Notes: Summary Dictyosome-like structures (DLS) of guinea pig spermatocytes, when prefixed in mixtures of glutaraldehyde and tannic acid, exhibited laminated figures with a repeating periodicity of about 4.5 nm in the spaces between DLS saccules or in association with the surfaces of the DLS saccules. These laminated figures were similar to those figures derived from saturated lipids in other tissues. Alternatively, spaces between saccules were collapsed leaving only thin, electron-dense material separating adjacent saccules. These changes were not observed when the DLS were prefixed in glutaraldehyde before exposure to tannic acid. The presence of laminated figures following fixation with tannic acid and osmium tetroxide suggests that saturated lipids are present in, or associated with, the intersaccular regions of the DLS. The distribution of laminated figures in other membrane structures was not affected by post fixation with tannic acid nor were laminated figures comparable to those of the DLS observed between cisternae of the Golgi apparatus. These results support previous conclusions that DLS are distinct from Golgi apparatus and are a unique component of the germ cell cytoplasm.

Notes: Summary The digestion of food in the heliozoonActinophrys sol is characterized by several distinct membrane events. Initially, extrusomes expand and fuse with each other and with the plasma membrane providing the membrane for the nascent food vacuole. During this process a—presumably lytic—material is secreted. After complete forming of the food vacuole a second type of vesicles fuses with it, whereupon usually lysis of the prey occurs. After denaturation and coagulation of the food, fluid is removed from the food vacuole. This process is accompanied by a high cytotic activity around the periphery of the food vacuole. Following this step, the perinuclear Golgi region shows an active appearance and numerous lysosomes fuse with the food vacuole. In consequence of this the food is degradated. The food vacuole shrinks continuously. Simultaneously vesicles filled with the digested material pinch off from the food vacuole, the content of which shows a more and more condensed mass of undigestible material. The undigestible residues are defecated eventually. The process of digestion is accompanied by an increase in volume and number of electron lucent cytoplasmic vacuoles. These vacuoles gradually become filled with a filamentous material starting with the vacuoles in the cell periphery. As the digestion continues, the vacuolar contents become condensed successively. Synchroneously the vacuoles move towards the cell center. After completion of the digestion, the cytoplasmic vacuoles decrease in volume and number and do not show any longer electron dense contents.

Notes: Summary Photooxidative bleaching of the CyanobacteriumAnacystis nidulans was studied by electron microscopic investigation of both freezefractured and thin-sectioned samples. During bleaching four consecutive phases in degradation of photosynthetic membranes (thylakoids) could be characterized: 1. No ultrastructural changes until photosystem II activity is lost. 2. Derangement of characteristic arrangement of thylakoids. 3. Thylakoids visible only in thin-sectioned but not in freeze-fractured samples. 4. Completely bleached cells, only traces in place of former thylakoids visible in thinsectioned samples. Bleaching did not cause lysis of the cells showing that the cytoplasmic membrane was not damaged. Polyhedral bodies also were still detectable in bleached cells.

Notes: Summary Using a formalin fixation technique whole chromosomes from root tips ofVicia species were isolated into a buffer solution. Combining this technique with the use of a set of reciprocal translocations available for this species—Vicia faba— allowed each member of the karyotype to be isolated and identified. Such isolated chromosomes can be used for optical microscopy or for either transmission or scanning electron microscopy where critical point drying clearly reveals chromatin fibre.

Notes: Summary The structure and elemental composition of the granules which make up the parapharyngeal mass of the ciliateHomalozoon vermiculare are analyzed. The mass is made up of two kinds of granules. One is not membrane-bounded and is composed of paraglycogen. The second type is comprised of concentric lamellae. It is rich in magnesium, phosphorus, potassium, and calcium. These results do not support the contention that the granules are directly involved in the process of food vacuole formation. The role of the parapharyngeal mass remains obscure.