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The manual gravimetric drying moisture determination methods currently employed by most mineral processing plants fail to provide timely and accurate information required for automatic control. The costs associated with transporting and handling concentrates still represent a major portion of the overall treatment price. When considering the cash flow of a mining operation that is governed by both the smelter contract, with moisture penalties and the quantity and quality of the concentrates shipped, an efficient method of on-line moisture content would be a welcome tool. A novel on-line determination system for ore concentrate moisture content would replace the tedious manual procedure. Since the introduction of microelectronic-based control systems, operators have strived to reduce the treatment costs to the minimum. Therefore, a representative and timely determination of on-line moisture content becomes vital for control set points and timely feedback. Reliable sensors have long been on the 'wish list' of mineral processors since the problem has always been that you can only control what you can measure. Today, the task of moisture determination is still done by the classical technique of loss in weight utilizing uncontrolled procedures. These same methods were introduced in the earliest base metal concentrators. Generally, it is acceptable to have ore concentrate moisture content vary within a range of 7-9%, but controlling the moisture content below 8% is a difficult task with a manually controlled system. Many times, delays in manually achieving reliable feedback of the moisture content results in the moisture varying from 5-12% before corrective actions can be made. This paper first reviews the traditional and widely available methods for determining moisture content in granular materials by applying physical principles and properties to measure moisture content. All methods are in some form affected when employed on mineral ore concentrates. This paper introduces and describes a novel on-line moisture sensor employed for mineral processing de-watering applications, which not only automates the tedious tasks but also results in reliable moisture feedback that can be used in the optimization of the de-watering process equipment such as pressure or vacuum filters and fuel-fired driers. Finally, two measurement applications will be presented which indicate the usefulness and summarizes the measurement requirements for the proposed method of employing drag force and mechanical properties of the material itself to determine the moisture content., (Copyright 2002 Elsevier Science Ltd.)

This study was undertaken to determine whether a mRNA for glial fibrillary acidic protein (GFAP) was present in increased amounts as a response to injury and, if so, how was its temporal expression related to the demonstration of GFAP by immunocytochemical techniques. A cerebral freeze-injury was produced in mice and at intervals thereafter the animals were anesthetized, perfused with formalin and histological sections of the brain through the injured area were prepared. A riboprobe for GFAP mRNA labeled with S35 and an immunocytochemical probe for GFAP were utilized to localize mRNA and GFAP immunoreactivity, respectively. For mRNA studies, the histological slide exposed to either sense or antisense probe was overlaid with x-ray film or dipped in photographic emulsion. The developed film was quantitated by digital image analysis. Emulsions were examined by dark-field microscopy. The results indicate that mRNA for GFAP is increased in the cortex in the environs of the injury by 6 hours, becomes maximal at 4-5 days, and is present in increased amounts up to 14 days. The message is enhanced in the adjacent cortex, the subpial region, the adjacent corpus callosum and in the ipsilateral and contralateral callosal radiations. This pattern of enhancement follows the distribution of post-injury edema. Glial fibrillary acidic protein is demonstrable at 24-48 hours after injury. Thus, there is a rapid response of the astrocyte to injury with increased mRNA expression that is followed by expression of GFAP immunoreactivity.

Morbidity caused by brain dysfunction affects more than 50 million persons in the United States. Although new neuropharmaceuticals have the potential for treating specific brain diseases, they may not effectively enter brain from blood. Safe strategies are needed for drug delivery through the brain capillary wall, which makes up the blood-brain barrier in vivo. Two of these strategies are reviewed, as are related new developments in the molecular and cell biology of the brain capillary endothelium. The production of chimeric peptides represents a physiologic-based strategy for drug delivery. It entails the covalent coupling of the neuropharmaceutical to a brain transport vector, allowing transportation through the blood-brain barrier. Another strategy is biochemical opening of the blood-brain barrier: intracarotid leukotriene infusion is a method for selectively increasing blood-brain barrier permeability in brain tumors without affecting barrier permeability in normal brain tissue.

A new method to study the interaction of astrocytes and pericytes with cerebral capillary endothelial cells in vitro is described. Endothelial cells derived from bovine brain were cultured on gelatin coated slides and covered with type 1 collagen. Endothelial cells aggregated and formed capillary-like structures (CS) within 3 days. The lining cells of the CS stained immunohistochemically for factor VIII-related antigen. Astrocytes isolated from neonatal mice or pericytes from bovine brain were added to the preparations after the formation of CS. After various periods of co-culture, the slides were fixed with methanol and examined with the immunohistochemical stain for glial fibrillary acidic protein or smooth muscle actin to demonstrate astrocytes or pericytes respectively. Five hours after addition, only 10% of astrocytes were associated with CS. However, by 24 hours, 70% of the astrocytes had assumed a position adjacent to the CS. The astrocytes then developed processes which were intimately apposed to the CS by 3 days, at which time they resembled the in vivo structural relationship between astrocytes and microvessels that occur in areas of central nervous system injury. Progressive elongation of the astrocytes or their processes at the CS was evident at 6 and 9 days of co-culture. The cross-section of CS co-cultured with astrocytes showed continuous cells surrounding a lumen, and the endothelial cells appeared to be connected by tight junctions. When pericytes were added to CS cultures they also preferentially associated with CS, but the contact occurred more rapidly than with astrocytes, 50% being associated with CS by 5 hours. The CS were almost completely covered with elongated pericytes by 24 hours. A chemotactic assay was developed that showed that there was a chemotactic attraction of pericytes to the CS. Thus an in vitro system is now available to study the interrelationships of these cell types and their interaction in development, regeneration and differentiation of the blood-brain barrier.

Conditioned medium from isolated cerebral capillary endothelial cells (ECCM) was found to promote DNA synthesis in astrocytes and pericytes, but not in oligodendrocytes or endothelial cells (EC) in vitro. The astrocyte was the cell of primary interest and the cell tested in the following experiments. The effect of ECCM on astrocytes was concentration and time dependent. The growth factor was released by EC into the medium in a cumulative manner for up to 72 hours. This release was not the result of a nonspecific leakage of an internal store, since the DNA synthetic activity of cell lysates was negligible. The growth factor secretion per cell was higher in sparse than in confluent EC cultures and was partially inhibited by preincubation of EC with interleukin-1. The DNA synthetic activity was due to a peptide, different from basic fibroblast growth factor, transferrin, bovine fibronectin and platelet derived growth factor, with a molecular weight greater than 50,000. The peptide derived from the cerebral capillary EC could be involved in the local signaling between cell types that control new vessel formation in development, in regeneration after brain tissue injury, or in tumor formation.

A passage of choline from blood to brain and vice versa has been demonstrated in vivo. Because of the presence of the blood-brain barrier, such passage takes place necessarily through endothelial cells. To get a better understanding of this phenomenon, the choline transport properties of cerebral capillary endothelial cells have been studied in vitro. Bovine endothelial cells in culture were able to incorporate [3H]choline by a carrier-mediated mechanism. Nonlinear regression analysis of the uptake curves suggested the presence of two transport components in cells preincubated in the absence of choline. One component showed a Km of 7.59 +/- 0.8 microM and a maximum capacity of 142.7 +/- 9.4 pmol/2 min/mg of protein, and the other one was not saturable within the concentration range used (1-100 microM). When cells were preincubated in the presence of choline, a single saturable component was observed with a Km of 18.5 +/- 0.6 microM and a maximum capacity of 452.4 +/- 42 pmol/2 min/mg of protein. [3H]Choline uptake by endothelial cells was temperature dependent and was inhibited by the choline analogs hemicholinium-3, deanol, and AF64A. The presence of ouabain or 2,4-dinitrophenol did not affect the [3H]choline transport capacity of endothelial cells. Replacement of sodium by lithium and cell depolarization by potassium partially inhibited choline uptake. When cells had been preincubated without choline, recently transported [3H]choline was readily phosphorylated and incorporated into cytidine-5'-diphosphocholine and phospholipids; however, under steady-state conditions most (63%) accumulated [3H]choline was not metabolized within 1 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Drug and solute transport through in vitro and in vivo models of the blood-brain barrier (BBB) were compared to provide a measure of how well the in vitro model predicted BBB permeability found in vivo. The in vitro model employed bovine brain capillary endothelial cells in either primary tissue culture or as a continuous line grown on Transwells and placed in side-by-side diffusion chambers. The in vivo model of BBB transport utilized an internal carotid artery perfusion/capillary depletion method in anesthetized rats. BBB permeability in vivo and in vitro was measured for 15 radiolabeled drugs and for L-[3H]dopa, D-[14C]glucose and [3H]albumin. [3H]- or [14C]sucrose was used in vivo as a blood volume reference. Lipid solubility of each drug was measured based on the 1-octanol/Ringer's partition coefficient. The morphology of the endothelial cell in primary tissue culture was spindle-shaped and the morphology of the endothelial cell in continuous culture was cuboid-shaped. The cuboidal morphology demonstrated a 2-fold greater resistance to solute transport and was used for the majority of the in vitro studies. Drug and solute permeability coefficients (Pe) ranged from 3.9 X 10(-3) to 2.5 X 10(-1) cm/min in vitro and from 1.0 X 10(-5) to 2.1 X 10(-2) cm/min in vivo. The In of the permeability.surface area product in vitro correlated with the In partition coefficient (r = 0.62, P less than .0125) and the In permeability.surface area product in vivo correlated with the In partition coefficient (r = 0.84, P less than .0005).(ABSTRACT TRUNCATED AT 250 WORDS)

Malignant astrocytoma of leptomeningeal origin is a rare central nervous system neoplasm. A study of surgical and autopsy material from a primary leptomeningeal malignant astrocytoma of the spinal cord is presented. The initial presentation was focal; an extramedullary, intradural mass caused thoracic cord compression, although at autopsy the neoplasm involved the entire leptomeninges. The histological, ultrastructural and immunocytochemical findings of a tumor in this location and its histogenesis are discussed.

Muscle samples for cultures were obtained from the quadriceps by open biopsy under local anesthesia in five patients with early stage of Duchenne muscular dystrophy (DMD) and 10 controls. Primary cultures were grown in Eagle's Minimum Essential Medium (MEM) with 20 per cent fetal calf serum. After 4 weeks, cells were trypsinized, counted, subcultured for 5 days in MEM with 5 per cent horse serum and finally incubated for 4 h with (3H) leucine. Ttal protein synthesis showed a significant decrease (half of control values) only in muscle cultures from patients with DMD. Addition of calclium chloride alone or with A23187 ionophore normalized this defect in protein synthesis. By contrast, myosin heavy chain synthesis was measured and found normal in all paitents.

Microvessels isolated from mouse forebrain were used as the source material for the derivation of cerebral vascular endothelium and smooth-muscle cells in culture. The microvessels were isolated by a mechanical dispersion and filtration technique, and were maintained in vitro as organoid cultures. A microvessel classification system was developed and proved to be useful as a tool in monitoring culture progress and in predicting the type(s) of microvessel(s) that would give rise to migrating and/or proliferating cells. The isolated cerebral microvessels were heterogeneous in diameter, size of individual vascular isolate, and proliferative potential. The isolated microvessels ranged in diameter from 4 micron to 25 micron and in size from a single microvascular segment to a large multibranched plexus with mural cells. The initial viability, determined by erythrosin B exclusion, was approximately 50% on a per cell basis. All microvessel classes had proliferative potential although the rate and extent of proliferation were both microvessel class- and density-dependent. The smaller microvessels gave rise to endothelial cells, whereas the large microvessels gave rise to endothelial and smooth-muscle cells. The viability and progress of a microvessel toward derived cell proliferation seemed to be directly proportional to the number of mural cells present.

Neoplastic angioendotheliosis is a rare disorder characterized by intravascular neoplastic proliferation of endothelial cells within vessels of all caliber in the meninges and neuropil. Ischemic infarcts of brain and spinal cord result from occlusion of the lumina by neoplastic cells of fibrin thrombi. Transition from reactive to neoplastic endothelium can be identified in many vessels. Steroid therapy can be beneficial in reduction of severity of symptoms, but cannot alter the course of disease. Therapeutic intervention must be undertaken promptly after the diagnosis is confirmed by meningeal and cortical biopsy if the inexorable course of the disease is to be altered.

Excellent correlation between computerized axial tomographic (CT) scans and the location and extent of pathologically verified intracerebral hematomas was demonstrated in eight patients. Superficial and intraventricular extension, hydrocephalus, and mass effect were easily identified; CT scanning was superior to angiography and radionuclide brain scanning in diagnosing hematoma and in determining its extent and associated ventricular size. Angiography was superior to CT scanning in demonstrating aneurysms and arteriovenous malformations as a cause of intracerebral hematoma. Computerized axial tomographic scanning is also useful in following the resolution of hematomas and in guiding surgical intervention.

The effect of inorganic lead on two functions of cerebral microvessel endothelium, cell division and glucose analog uptake, was investigated. Lead concentrations considered to be toxic in humans inhibited both functions in cultured endothelial cells. Both effects were dependent on the length of lead exposure and dose over the range of 10(-4) to 10(-6) M lead acetate. After 4 days of exposure there were 76% fewer cells in 10(-4) M lead-exposed cultures relative to control cultures. After 4 days of exposure to 10(-5) M lead there were 55% fewer cells, and after 10(-6) M lead exposure there were 15% fewer cells. Two days after 10(-4) M lead exposure [methyl-3H]thymidine incorporation into endothelial cells was inhibited by 71%. Incorporation was inhibited 47% by 10(-5) M lead but 10(-6) M lead did not inhibit incorporation after 2 days of exposure. Glucose analog uptake was inhibited in both contact-inhibited and log-phase cells; however, the latter were more sensitive to lead and this increased sensitivity correlated with a higher lead content in this cell population. Both the specific carrier-mediated and the nonspecific components of glucose analog uptake were inhibited by exposure of the endothelial cells to lead. A lead exposure of 40 min produced a significant effect on the uptake mechanism. In order to manifest its effects the lead had to be present in serum-containing medium, suggesting that some serum component was necessary to present the lead to the endothelial cells. These findings imply that the initial target of inorganic lead in the CNS may be the plasma membrane of the capillary endothelial cells, and that lead may act by altering the physiological function of these membranes.

Two family members with hereditary pressure-sensitive neuropathy are reported. One patient presented atypically with acute brachial plexus neuropathy following transaxillary removal of the first rib. Electrophysiological studies showed slowing of motor nerve conduction in clinically affected and unaffected nerves. In vitro recording of the compound action potential of the subclinically involved sural nerve showed pronounced slowing in conduction of large and small myelinated fiber groups. These alterations correlated with morphological studies of the sural nerve that showed tomacula with acute and healed segmental demyelination. An inherited, generalized neuropathy manifested by a morphological abnormality of myelination may render peripheral nerves unduly susceptible to mechanical trauma, including positional pressure or traction effects during general anesthesia.

Although macrophages are the earliest cells found in association with vessels in an area of cerebral injury, the role of this cell in the subsequent regeneration of the microvasculature is unknown. DNA synthesis in cerebral endothelial cells at the margin of injury of mouse brain was assayed by quantitation of the labeling indices from 3H-thymidine autoradiographs of normal animals and animals with X-ray-induced leukopenia. A mean endothelial cell labeling index of 10% in the irradiated animals was significantly lower than control animals (26.7%) (p less than 0.01). In vitro tissue culture studies utilizing peritoneal macrophages and cerebral endothelium were then used to isolate the endothelial response to macrophages and their products. Macrophage-conditioned media did not stimulate cerebral endothelial proliferation when evaluated by a growth factor assay, although this macrophage-conditioned media did stimulate DNA synthesis in fibroblasts and bovine aortic endothelium. A migration study of the cerebral endothelial cells utilizing an agarose technique showed enhanced random migration in the presence of macrophage-conditioned media compared to controls (p less than 0.01). The results indicate that macrophages do not directly stimulate proliferation of cerebral endothelial cells, but influence their migration. A loss of contact inhibition and subsequent DNA synthesis and replication may follow.

Findings on cranial computed tomography (CT) were correlated with autopsy findings in 58 cases with 129 lesions to determine CT reliability. When only CT scans of good quality were considered, there were no false positive cases. The number of false negative studies varied directly with lesion size: one of 42 lesions larger than 2.5 cm; four of 12 lesions between 1.5 and 2.5 cm; 12 of 15 between 0.5 and 1.5 cm; and all 21 of those smaller than 0.5 cm. Lesion size was undetermined in the remaining 18 casesbecause of the nature of the disease. While the series is small, these results suggest that the current detector threshold for CT may be in the range of 0.5-1.5 cm, although smaller lesions may be seen if there is substantial surrounding edema.

Experiments were performed to test the hypothesis that insulin stimulates DNA synthesis in cerebral microvessel endothelium and smooth muscle. Cultured endothelium and smooth muscle derived from isolated mouse cerebral microvessels were exposed to insulin in serum-free medium, and [3H]-thymidine incorporation in the cells was measured. Up to 40-fold stimulation of DNA synthesis in endothelium and fourfold stimulation in smooth muscle were observed. Stimulation became maximal in both cell types at an insulin concentration of approximately 10(4) ng/ml, although an effect was observed at much lower concentrations. Similar concentrations of insulin produced a less-dramatic (approximately twofold) increase in both endothelial and smooth muscle cell numbers. This effect of insulin, observed in microvessel endothelium and smooth muscle, but not in bovine aortic endothelium, emphasizes another way in which large- and small-vessel endothelia appear to differ.

Adenosine uptake by cerebral smooth muscle cells is a carrier-mediated process. The Km value for adenosine uptake is 10.0 microM and the Vmax is 0.95 nmol/min-mg cell protein. This uptake system is inhibited by the adenosine analog 2-chloroadenosine at low adenosine concentrations. These results prove the existence of a nucleoside transport system associated with cerebral smooth muscle.

This is a report of an unusual, densely cellular, midcerebellar neoplasm in a seven-year-old boy. Although clinically consistent with a medulloblastoma, immunohistochemistry and electron microscopy demonstrated glial and rhabdomyoblastic differentiation in the tumor. We discuss the differential diagnosis of this tumor as it relates to glial differentiation in medulloblastomas and the myogenic potential of primitive neuroectoderm.

We studied four patients with peripheral neurofibromatosis and a neuropathy that had the clinical characteristics of peroneal muscular atrophy. Nerve conduction velocities were slowed by less than 40% of normal, and electromyography demonstrated denervation. Sural nerve biopsies from two patients, which were macroscopically free of nerve sheath tumors, were studied by recording the compound action potentials in vitro and by morphometry. These studies demonstrated a chronic axonal neuropathy with reactive Schwann cell changes. Peroneal muscular atrophy in association with neurofibromatosis may be due to progressive neuronal degeneration and may represent another, uncommon manifestation of peripheral neurofibromatosis.

Disulfiram is used to treat alcoholism and is known to cause peripheral neuropathy: few reports of biopsied human nerves have revealed axonal degeneration and loss of myelinated fibers. We studied a 22-year-old woman with severe sensorimotor neuropathy following treatment with disulfiram for 6 months. Histologic studies of the sural nerve revealed a neurofilamentous axonopathy with rare enlarged axons distended by neurofilaments. Disulfiram is converted enzymatically to carbon disulfide, which causes neurofilamentous distal axonopathy in animals. Similar changes in human nerve after disulfiram administration suggest that carbon disulfide is the toxic agent.

A causal relationship between paraproteinemia and neuropathies has been suggested. We studied three patients with chronic sensorimotor polyneuropathy associated with plasma cell dyscrasia and monoclonal gammopathies (IgGK, IgMK, IgA lambda). Sural nerve biopsies showed mild (2 cases) to moderate loss of myelinated fibers (1 case). Teased single fiber studies showed segmental demyelination-remyelination in two patients. Direct immunofluorescence demonstrated immune deposits of the myelin sheath of the same specificity as the serum paraprotein, IgGK (1 of 3 cases). Treatment with prednisone, melphalan or chlorambucil, and plasmapheresis resulted in remission (1 case), partial improvement (1 case), or had no effect (1 case), although reduction of monoclonal immunoglobulin occurred in all. To investigate the role the paraproteins might play in the pathogenesis of the neuropathy, patients' serum was injected intraneurally into rat sciatic nerves. None of the animals developed weakness, slowing of in vitro conduction of sciatic nerve, or significant evidence of demyelination by light- or electron-microscopy or teased single fiber studies 48 hours postinjection. Similar injections of rabbit serum with experimental allergic neuritis (EAN) produced focal segmental demyelination. Our studies employing an in vivo bioassay technique failed to establish antimyelin activity of monoclonal immunoglobulin sera.

The ultrastructural features of Bunina type inclusions in the anterior horn cells of a patient dying of amyotrophic lateral sclerosis with dementia appear unique. The Bunina-type inclusions are electron dense aggregates containing, and surrounded by organelle-like membranes. These inclusions appear to be a special type of autophagic vacuole, possibly arising from altered mitochondria.

An immunoperoxidase technique was utilized to identify herpes simplex type I viral antigens in the retina, optic nerve and brain of an adult with herpetic retinitis and encephalitis. Viral antigens were demonstrated in all layers of retina, retinal pigment epithelium and to a lesser extent, in choroid. Oligodendroglia in the right optic nerve and neuronal and glial cells in the grey and white matter of the left frontal, inferior parietal and temporal lobes of the brain also expressed herpes simplex antigens. The sensitive immunoperoxidase method allowed detection of viral antigens in many cells without intranuclear inclusions or surrounding inflammation, and thereby added valuable information regarding the anatomic and cellular localization of herpetic infection. The clinicopathologic features that characterize herpes simplex retinitis in the adult are compared to cytomegalovirus retinopathy.

The endothelia of microvessels isolated from mouse brain by mechanical means are rich in gamma-glutamyl transpeptidase; however, the enzyme often disappears when the cells migrate or proliferate from the microvessel isolates. In an endothelial cell line derived from similar isolates and negative for gamma-glutamyl transpeptidase, the enzyme could be induced in the endothelial cells when they were cocultured with glial cells. Thus there may be a requirement for continuous induction of gamma-glutamyl transpeptidase in brain microvessels by adjacent glial cells.

The distribution of S-100 protein and neuron-specific enolase (NSE) was examined in 19 meningiomas using the peroxidase-antiperoxidase (PAP) immunohistochemical technique. Positive cytoplasmic staining for NSE was observed in 16 tumors, and comparable staining for S-100 protein was observed in eight tumors. The finding of S-100 protein and NSE immunoreactivity in fibroblastic, meningiotheliomatous, and transitional meningiomas raises the possibility that these morphologically distinct neoplasms derive from a common pluripotential cell capable of differentiation along diverse paths.

Orbicularis oculi muscle biopsies were performed in 38 patients (ten with chronic progressive external ophthalmoplegia and 28 controls) to determine whether ragged red fibers were present and, if so, whether they were specific to progressive external ophthalmoplegia. To our knowledge, the orbicularis muscle has not been previously studied in this regard. Ragged red fibers were seen in the orbicularis oculi in patients with and without ophthalmoplegia, although they were more abundant in patients with ophthalmoplegia. The limb muscles of patients with ophthalmoplegia showed ragged red fibers. Electron microscopy demonstrated that these fibers contain either abnormal or increased numbers of normal mitochondria. Thus, the presence of ragged red fibers in the orbicularis oculi muscle is not limited to patients with chronic progressive external ophthalmoplegia, and the diagnosis of this disorder with ragged red fibers should be based on a combination of clinical and laboratory findings, including those from a limb muscle biopsy.

Optical Fourier methods of image processing coupled with mutual information analysis were applied to the separation of human muscle specimens into four diagnostic classes. This process allowed rapid, relatively inexpensive data acquisition, reduction, and classification. The accuracy of the method when compared to that of experienced surgical pathologists is acceptable. Difficulties arise when material outside of the previous experience of the computer is presented.

This study was undertaken to determine the effect of neutralization of brain endothelial cell luminal membrane anionic charge on endothelial permeability properties. Mouse brain microvessel endothelial cells were grown to confluence on a nitrocellulose filter. The permeability of the endothelium to Evan's blue dye (EBD) (molecular weight 960) and fluoresceinated dextran (FITC-D) (molecular weight 20,000), both polar molecules, was assessed before and after the exposure of the endothelium to cationic ferritin (CF) or native ferritin (NF). The use of CF resulted in a significant increase in permeability of the endothelium to EBD compared to NF. This result indicates that ablation of endothelial surface anionic charge enhances endothelial transport of a small, polar-charged molecule. Cationic ferritin did not increase the permeability of FITC-D compared to NF. This negative result is not surprising because FITC-D differs from EBD in terms of charge and solubility as well as in size. The electrical resistance of the endothelial cell layer after the application of CF was unchanged from baseline values suggesting a transcellular rather than a paracellular route of the EBD leakage.

A patient who was partially immune to tetanus developed nonfulminant tetanus after a minor injury. Manifestations of the disease persisted for over 17 months. Electrophysiologic studies revealed an absent silent period in the masseter muscle, large-amplitude F-responses, and denervation. A muscle biopsy showed neurogenic atrophy with reinnervation. This observation supports the existence of chronic tetanus and provides morphologic evidence for a peripheral action of tetanus toxin in humans.

The purpose of this study was to assess the morphologic effects of antiendothelial antibodies (EAB) on mouse brain endothelium in vivo. The antigen utilized was the plasma membranes fraction of cultured mouse brain endothelial cells, which was injected into rabbits with complete Freund's adjuvant. The resultant antibody-containing serum was injected back into mice via tail veins in varying time courses and dosages, followed by perfusion of the animals. The antibody was primarily IgG, and was visualized on the brain endothelium by electron microscopy, using the peroxidase antiperoxidase (PAP) labeling technique. Normal rabbit sera and saline were used as controls. Results showed a significantly greater number of micropinocytotic vesicles in the endothelium of the test animals compared to controls. The number of multivesicular bodies and the thickness of the endothelium were also greater in the test animals. At no time was antibody visualized internal to the endothelial luminal membrane, and no lesions such as inflammation or necrosis were observed. This study shows that serum-containing antiendothelial antibodies has a direct, but apparently limited, effect on endothelium.

An A and L system of neutral amino acid transport has been demonstrated previously in cerebral microvessels in vivo and in isolated microvessels in vitro. This report describes the neutral amino acid transport properties of cultured cerebral endothelial cells and investigates the influence of astroglia on the transport process. These studies confirm the presence of a sodium-dependent A-system and a sodium-independent L-system of neutral amino acid transport in cultured cerebral endothelial cells. The A-system transport is slower than L-system transport and each is variably inhibited by other amino acids. Transport is enhanced in log phase cells as compared to stationary phase contact-inhibited cells. Contact with glial cells or exposure to glial-conditioned media enhances neutral amino acid transport. These in vitro studies indicate that the A- and L-systems of neutral amino acid transport are in a dynamic state and are influenced by the phase of cell growth and contact with astroglia.

Polarity has been shown to exist at the blood-brain barrier (BBB) with respect to Na+-dependent neutral amino acid transport. A situation similar to the endothelial-astrocyte relationship existing at the BBB can be produced by growing cultured cerebral endothelium on one side of a filter and C6 glial cells on the other in an enclosed double chamber. In this setting 3H-alpha-methylaminoisobutyric acid transport can be demonstrated and is more rapid from the glial surface across the endothelium, as compared with transport in the opposite direction. The observation supports a glial influence on BBB polarity in this system.

To predict clinical outcome, we studied 42 paragangliomas from 37 patients by routine histology, immunohistochemistry, and electron microscopy. A panel of antisera to neuron-specific enolase (NSE), chromogranin, and met-enkephalin was used to identify chief (type I) cells, and S-100 protein and glial fibrillary acid protein (GFAP) sustentacular (type II) cells. The intensity of staining of type I cells and the density of type II cells were assessed semiquantitatively (0 to 4+) in a total of 38 tumors. A total of 23 of 24 low-grade tumors (solitary, multiple, or associated with other neoplasms; 95.8%) contained type II cells immunoreactive with either S-100 protein or GFAP, and all were positive when S-100 protein and GFAP were used in combination. Five of the nine intermediate-grade (recurrent and/or locally aggressive) tumors were identified as glomus jugulare tumors (GJT). Three intermediate-grade GJTs were devoid of GFAP-reactive type II cells and four GJTs were negative for S-100 protein. Type II cells were identified in only one of five high-grade (malignant) paragangliomas and that tumor contained vanishingly rare cells that were weakly S-100 protein positive but GFAP negative. Sustentacular cell density and chief cell staining intensity were both inversely related to tumor grade. The most sensitive chief cell marker was NSE (92.1%), followed by chromogranin (84.2%). The least sensitive (73.0%) and specific marker was met-enkephalin. Combinations of NSE or chromogranin with met-enkephalin identified chief cells in all cases. Electron microscopy identified neurosecretory granule-containing chief cells, but was of less value in delineating sustentacular cells because of their scarcity and the absence of specific features. By comparison, immunohistochemistry was superior in identifying sustentacular cells. The use of an immunohistochemical panel, in addition to routine histology, can confirm the diagnosis of a paraganglioma and can give an indication of the likely prognosis for a patient.

A case report of malignant external otitis is presented with particular emphasis on the neuropathological sequelae. The most striking finding was a mycotic aneurysm of the basilar artery with resultant thrombosis and brain stem infarction. Diffuse pachymeningitis was also present. The severity of the changes described in this case further point out the need for early recognition and adequate treatment of this potentially fatal disease complex.

A spontaneously-occurring spongy disorder of the white matter of the central nervous system was discovered in the Charles River strain of Swiss-Webster mice and is described in this report. The disorder was transmitted with an autosomal recessive pattern of inheritance. Clinical characteristics of the affected animals included enlargement of the cranium, failure to thrive and tremor of the hind limbs when held by the tail in a suspended position. Maintenance of the colony with propagation of the disease was achieved by selective in-breeding of litter mates. Light microscopic examination of the central nervous system revealed a spongy degeneration of the white matter of the entire neuraxis. Ultrastructural studies localized the abnormality to the cell body and processes of the astrocyte which appeared distended and enlarged with dispersion of cytoplasmic organelles. Hemidesmosomes were prominent in the foot processes of astrocytes. This animal model bears a similar morphology and pattern of inheritance to Canavan's spongy degeneration of the white matter in humans and should provide a base for future investigations aimed at gaining insight into the pathogenesis of the human and this animal neurological disorder.