Nachweis und Verteilung der Enzyme: β-d-Glucuronidase, β-d-Galaktosidase, β-d-Glucosidase und Arylsulfatase in Neurinomen

Zusammenfassung In 17 Neurinomen wurden Verteilung und Aktivität der hydrolytischen Enzyme -d-Glucuronidase, -d-Glucosidase, -d-Galaktosidase und Arylsulfatase untersucht.Die höchste Aktivität der Enzyme zeigten die verfetteten Neurinome. Es bestand eine enge Beziehung zwischen Lipidablagerung und Fermentaktivität.Daraus wurde geschlossen, daß die im Neurinom gebildeten Markscheidenlipide unter Mitwirkung der untersuchten Hydrolasen abgebaut werden.

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Demonstration and distribution of the enzymes: -d-glucuronidase, -d-galactosidase, -d-glucosidase, and arylsulfatase in neurinomas

Summary In 17 neurinomas, distribution and activity of the hydrolytic enzymes -d-glucuronidase, -d-glucosidase, -d-galactosidase, and arylsulfatase were examined. Highest enzyme activity was seen in neurinomas stuffed with lipid material. There was close relationship between lipid deposition and enzyme activity. From these findings it was concluded that myelin lipids formed in neurinomas are degradated by means of the examined hydrolases.

     

Ultrastructural localization of lectin receptors on cerebral endothelium

Summary Oligosaccharide residues on the endothelial luminal plasma membrane of rat cerebral cortical vessels were localized using biotinylated lectins. In addition, the effect of pretreatment of brain slices with neuraminidase prior to the binding of cationized ferritin (CF) and certain lectins was studied.Conjugates of biotinylated lectins and avidin-d horseradish peroxidase reaction product were evenly distributed on the endothelium of arterioles, capillaries, and venules. Lectin binding sites were observed on the plasma membrane of pinocytotic vesicles open onto the vascular lumen and at the luminal end of the interendothelial space only. The following sugar residues were localized: -d-mannosyl, -d-glucosyl, -N-acetylglucosaminyl, sialyl,d-galactosyl, -l-fucosyl, and -N-acetyl-d-galactosaminyl.Following pretreatment of brain slices with neuraminidase -d-gal-(1–3)-d-galN-acetyl groups were demonstrated on endothelium. In this respect, cerebral endothelium differs from noncerebral endothelium which is reported to have peanut agglutinin binding sites without neuraminidase pretreatment.Anionic groups on cerebral endothelium were demonstrated at the same locations as the lectin binding sites. Following neuraminidase pretreatment there was reduction, but not absence, of CF binding supporting the observation that surface charge is not wholly due to sialyl groups.The role of monosaccharide residues in states of altered cerebrovascular permeability remains to be determined.Supported by Ontario Heart Foundation grant no. 2-6     

Lectin histochemistry of scrapie amyloid plaques

Summary Peroxidase-labeled lectins were used for detection of specific monosaccharide residues in amyloid plaques in brains of scrapie-infected mice. The lectins tested recognize the following residues: -d-galactosyl (Ricinus communis agglutinin 120, RCA-1), -d-galactosyl and -d-galactopyranoside (Bandeirea simplicifolia aggl., BSA), -d-mannosyl and -d-glucosyl (Concanavalin A, Con A), N-acetylglucosaminyl and sialyl (Wheat germ aggl., WGA), sialoglycoconjugates (Limulus polyphemus aggl., LPA), -l-fucosyl (Ulex europeus aggl., UEA-1 and Tetragonolobus aggl., TPA), N-acetyl-d-galactosaminyl (Helix pomatia aggl., HPA). The most intense staining reaction in amyloid plaques was observed with BSA and WGA; it was less intense with RCA-1, Con A, and HPA. This indicates that the plaque material contains glycoproteins with abundance of accessible residues of - and -galactose, N-acetyl-d-glucosamine and N-actyl-d-galactosamine, and some types of sialoglycoconjugates recognized by WGA. Such residues, like -l-flucosyl recognized by UEA-1 and TPA, were almost undectectable in the examined plaques.There were also some differences in the staining intensity between small and large plaques (WGA and HPA) and between central and peripheral areas of the plaques.In the wall of micro-blood vessels relatively strong staining reaction was observed with RCA and BSA and less intense with WGA and Con A.Support in part by grant no. 5PO1 AG 04220-03 from the National Institute of Aging, NIH     

Cerebral endothelial plasma membrane alterations in acute hypertension

Summary This study was undertaken to localize oligosaccharide residues on the endothelial luminal plasma membrane of cerebral vessels of normotensive animals and vessels permeable to horseradish peroxidase (HRP) in angiotensin-induced acute hypertension. Wistar-Furth rats were injected with HRP intravenously and hypertension was induced by an intravenous infusion of angiotensin amide. Animals were fixed 2.5, 10 and 15 min later and the HRP reaction product was demonstrated in brain slices, followed by lectin localization using the avidin-biotinperoxidase method. Oligosaccharide residues demonstrable on the luminal plasma membrane of cerebral endothelium of normotensive controls and both permeable and nonpermeable vessels of hypertensive animals were: -d-mannosyl, -d-glucosyl, -N-acetylglucosaminyl, sialyl, -d-galactosyl, -l-fucosyl and -N-acetyl-d-galactosaminyl groups. Peanut agglutinin did not bind to the endothelium of normotensive controls or of nonpermeable vessels in hypertensive animals, but did bind to endothelium of vessels permeable to HRP 2.5 min after the onset of hypertension. At 10 min, the luminal plasma membrane of vessels regained their normal characteristics and peanut agglutinin binding was no longer demonstrable. Our studies suggest that increased cerebrovascular permeability to protein in acute hypertension is associated with loss of the terminal sialic acid groups on the luminal plasma membrane of permeable vessels. This results in the observed reduction of charge on the endothelium and an exposure of -d-gal-(1,3)-d-gal N-acetyl groups leads to binding of peanut agglutinin. Both alterations are rapidly reversible and no longer demonstrable 10 min after the onset of hypertension, when blood pressures reach resting levels and the blood-brain barrier is restored.Supported by Heart and Stroke Foundation of Ontario Grant 2-6     

Changes in the distribution of endothelial surface glycoconjugates associated with altered permeability of brain micro-blood vessels

Summary Lectin-binding sites located on the endothelial cell (EC) surfaces in unaltered, leaking and resorbing micro-blood vessels (MBVs) in cryo-injured cat brain were studied. Lectin or glycoprotein-gold complexes and brain samples embedded in hydrophilic resin Lowicryl K4M were used. The lectins tested recognize the following residues: -d-galactosyl (Ricinus communis agglutinin 120, RCA and peanut agglutinin, PNA), sialyl (Limax flavus agglutinin),N-acetyl-d-galactosaminyl (Helix pomatia agglutinin and soybean agglutinin, SBA), -d-glucosyl and -d-mannosyl (concanavalin A). The luminal front was labeled with SBA, and both fronts of the EC were labeled with PNA only after neuraminidase digestion. The most abundant and regularly distributed on both fronts of the EC were -d-galactosyl residues (RCA). These residues were also most affected in altered MBVs. The labeling of sialic acid residues was less pronounced on both sides of the EC. Following alteration of the function of the blood-brain barrier by cold-lesion injury, in leaking MBVs which represent increased luminal transport, we observed a conspicuous diminution of the labeling of the luminal surface of the EC with some lectins. On the other hand, in resorbing blood vessels located in the area of edema, where a presumably reverse (abluminal) transport occurs, major changes in the distribution of lectin-binding sites occurred on the abluminal front of the EC and in the basement membrane. The results reported here indicate that luminal and abluminal fronts of the EC change their properties in various functional conditions of MBVs, and that these changes can also be a reflection of functional polarity of brain endothelium.Supported in part by a grant from NINCDS no. 17271-05     

Effect ofd,l-α-aminoadipate on the mediobasal hypothalamus and endocrine function in the rat

Summary Using the glutamate analog,d,l--aminoadipic acid (d,l-AA), experiments were conducted to examine the nature, extent, and specificity of its toxicity in the mediobasal hypothalamus and to determine its effect on endocrine homeostasis. Neonatal rats received daily injections ofd,l-AA (4 g/kg BW) on postnatal days 5–10 and were killed at various post-treatment intervals. Sex-matched littermates were given equimolar amounts of NaCl and served as controls. Treated rats killed 18 days post injection weighed slightly less than controls and had reduced testicular, ovarian, and uterine weights, but the differences were not statistically significant. Ind,l-AA treated rats serum and pituitary levels of TSH and PRL were comparable to control values. Pituitary content of LH ('s and 's) and FSH ('s), however, was lower (P<0.05) ind,l-AA treated rats than in controls, but serum levels were not significantly different. Distinct cytopathologic changes were evident in the arcuate nucleus and median eminence ofd,l-AA-treated rats killed at 2 and 6 h post injection only. By 12 h evidence of acute damage had largely disappeared. Both glial and ependymal cells underwent edematous swelling and necrosis, but neurons were largely unaffected. Evidence of reactive changes, such as gliosis, infiltration of microglia, and removal of debris, however, were not very conspicious. A random sample of mediobasal hypothalami of rats killed 18 days post injection failed to show any detectable lesion or residual effects of earlier pathology. Age at the time of exposure to the gliotoxin was found to be an important variable affecting both extent and duration of injury. The most deleterious effects were observed when the gliotoxin was administered in the form of a single injection on postnatal day 5 only. The results suggest that normal neuronal activity and endocrine homeostasis, specifically gonadotropin, may be irreversibly altered as a consequence of transient disruption of the glial compartment.Supported by grants from the Medical Research Council of Canada, the St. Boniface General Hospital, and Mrs. James A. Richardson Research Foundations     

Lectin histochemistry of gangliosidosis

Summary Lectin histochemical studies were performed on selected formalin-fixed, paraffin-embedded tissues of patients affected with the O variant of G_M2-gangliosidosis (i.e., Sandhoff's disease). The purpose was to identify specific sugar residues of undegraded stored substances in cytoplasm of affected cells. We studied neural tissues from 13 patients, visceral tissues from four patients, and placentae from three affected fetuses. Neurons in all 13 cases studied stained withConcanavalia ensiformis agglutinin (Con A) and withUlex europaeus agglutinin-I (UEA-I). Succinylated wheat germ agglutinin (S-WGA) stained affected visceral cells and astrocytes and macrophages in the central nervous system. These results demonstrate that -d-mannosyl and -l-fucosyl residues, which bind Con A and UEA-I, respectively, are present in affected neurons. Furthermore, they revealed the affected nonneuronal cells and astrocytes contain complex carbohydrates with nonreducing terminal -N-acetylglucosamine, which binds S-WGA.Supported by grant NS 2176 from the National Institute of Neurological and Communicative Disorders and Stroke     

Beitrag zur Frage psychischer Störungen bei Eunuchoidismus

Zusammenfassung Es wird der Fall eines Mannes beschrieben, der durch tuberkulöse Erkrankung im Alter von 35 Jahren zuerst den linken Hoden und Nebenhoden durch Operation verlor, dann 5 Jahre später aus der gleichen Ursache auch den rechten Nebenhoden und Teile des rechten Hodens. Kurz vor der zweiten Operation trat eine paranoide Störung auf mit dem Gefühl, unter Hypnose zu stehen, imaginäre Befehle ausführen zu müssen, beobachtet und verfolgt zu werden usw. Bei der Untersuchung fand sich eine deutliche Gynäkomastie. Auch bei einer 2 Jahre später auftretenden psychischen Störung ähnlicher, aber schwächerer Symptomatik waren schizophrene Störungen nicht erkennbar. Es handelte sich vielmehr um ein endokrines Psychosyndrom (M. Bleuler), bei dem passagere, wahnhafte Phasen auftraten. Diese Störungen werden in Parallele gesetzt zu E. Kretschmers psychogener Wahnbildung bei traumatischer Hirnschwäche und gedeutet als eine Abart des sensitiven Beziehungswahns (E. Kretschmer), wobei unter Selbstwahrnahme der verminderten seelischen Leistungsfähigkeit sowohl die körperliche (cerebrale) Beeinträchtigung durch endokrine Gestörtheit als auch die dabei stattfindende Verarbeitung von Erlebnissen als entscheidend angesehen werden für das Zustandekommen der wahnhaften Erlebnisvorgänge.An Hand dieses Falles wird die Schwierigkeit der begrifflichen Trennung von Psychose und Neurose diskutiert.     

Immunohistochemical study on the distribution of α and β subunits of S-100 protein in brain tumors

Summary The immunohistochemical distribution of and subunits of S-100 protein (S-100, S-100, respectively) in 138 cases of human brain tumors was investigated by the avidin-biotin immunoperoxidase method. Brain tumors can be divided into four groups: group 1 [S-100 (+) and/or S-100 (+)]; astrocytoma, glioblastoma, ependymoma, subependymoma, oligodendroglioma, choroid plexus papilloma, gangliocytoma, meningioma, chordoma, malignant melanoma. Group 2 [S-100 (+) and S-100 (-)]; pineoblastoma, pituitary adenoma, craniopharyngioma, rhabdomyosarcoma. Group 3 [S-100 (-) and S-100 (+)]; acoustic Schwannoma. Group 4 [S-100 (-) and S-100 (-)]; medulloblastoma, malignant lymphoma, germinoma. The S-100 immunoreactivity pattern in brain tumors was similar to those obtained using conventional anti-S-100 protein sera. In the first group of brain tumors both the number of positively stained tumor cells and the staining intensity were generally greater for S-100 than for S-100 with a few exceptions including one gemistocytic astrocytoma, one subependymoma, one malignant melanoma, and some cases of glioblastomas. As to the relationship between malignancy and S-100 protein in glioma, S-100 immunoreactivity decreased according to degree of malignancy, while that of S-100 varied, suggesting a heterogeneity of tumor cells in glioblastomas. Immunostaining for S-100 and S-100 might become a useful diagnostic procedure in brain tumors and may give us more detailed and precise data of S-100 protein in brain tumors.     

Über den Nachweis „spezifischer“ Proteine im Liquor cerebrospinalis durch die Immunoelektrophorese

Zusammenfassung Im normalen Liquor cerebrospinalis lassen sich mit der Immunoelektrophorese unter Anwendung spezieller Antiliquoreseren zwei liquor-spezifische Proteine nachweisen, die von Dencker als -CSF und -CSF bezeichnet wurden. Auch durch erschöpfende Absorption des Antiliquorserums mit menschlichem Serum lassen sich Antikörper gegen diese liquorspezifischen Proteine aus dem Antiserum nicht entfernen. Das -CSF stellt sich in der Immunoelektrophorese nach Scheidegger als lang ausgestreckte Linie in der Nähe des Antikörpergrabens dar, das -CSF verläuft geschwungener und in der Hälfte der Fälle in einem Doppelbogen ähnlich dem des Transferrins.In 90 untersuchten Seren wurden diese Linien in keinem Falle angetroffen. Von 278 teils normalen, teils pathologisch auffälligen Liquores enthielten 26 kein -CSF, und bei 7 dieser 26 Liquores fehlte auch die -CSF-Linie. Die Mehrzahl der 26 Liquores war auch sonst pathologisch verändert, ohne daß eine Beziehung zwischen Zellzahl, Gesamteiweiß und -Globulingehalt zu dem Verhalten der liquorspezifischen Proteine hergestellt werden konnte.Zugaben von Serum zum Liquorkonzentrat vor der Immunoelektrophorese löschen das -CSF leichter als das -CSF aus. Ein Fehlen der liquorspezifischen Proteine in Liquores mit erhöhtem Eiweißgehalt oder Blutbeimengung kann damit erklärt werden. Bei anderen Liquores mit fehlender Nachweisbarkeit der -CSF- oder -CSF-Linie ist eine verminderte Produktion dieser Proteine zu erwägen.

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Summary By means of immunoelectrophoresis with specific Anti-CSF-sera, two proteins specific for the cerebrospinal fluid, named -CSF and -CSF by Dencker, can be demonstrated. Antibodies reacting with CSF-specific proteins are not abolished even after extensive absorption of the anti-CSF-serum with human serum as antigen. -CSF-proteins show up as a long smooth band close to the center groove when separated by immunoelectrophoresis according to Scheidegger. The bands of -CSF-proteins are more curved and in 50% of all cases form a double band similar to that of transferrin.These bands were not detectable in 90 serums examined. 26 out of 278 normal and pathological specimens of CSF failed to show any -CSF. The -bands were missing in 7 of these 26 specimens. The majority of these 26 specimens revealed additional pathological laboratory findings. No relation, however, appeared to exist between the presence or absence of CSF-specific proteins, cell count, total protein and -globulin.Upon the addition of serum to the concentrated specimens of CSF prior to immunoelectrophoresis, -CSF bands are eliminated more easily than the -CSF-bands. This could explain the absence of CSF-specific proteins in specimens with elevated protein or containing blood. However, a diminished production of proteins should also be considered when - and -CSF-proteins are absent.

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Wir danken Frau Sigrun Bach und Fräulein Christa Wackler für ihre sorgfältige technische Mitarbeit.     

Ganglioside mapping of a human medulloblastoma xenograft

Summary The ganglioside patterns of medulloblastomas have never been established; in this study we report the ganglioside profile of the human medulloblastoma cell line TE-671 grown as a xenograft in nude mice. Gangliosides were isolated and structurally analyzed by fast atom bombardment mass spectometry following permethylation. Identification of individual gangliosides was also performed by immunostaining of high-performance thin-layer chromatography-separated bands. Total ganglioside levels of 0.20 mol/g of tissue were obtained, consistent with those reported for human glioma cell lines grown as xenografts; predominant monosialogangliosides of TE-671 xenografts were II³--NeuAc-LacCer (GM3) and II³--NeuAc-GgOse₃ Cer (GM2) but there were also relatively large proportions of IV³--NeuAc-LcOse₄Cer (3-isoLM1), IV³--NeuAc-nLcOse₄Cer (3-LM1) and a further ganglioside of the neolactoseries with an extra lactosamine moiety. The only oligosialoganglioside detected was IV³, II³--NeuAc₂-GgOse₄Cer (GD1a).Abbreviations: The gangliosides have been designated according to Svenerholm [18] GM3 II³--NeuAc-LacCer - GM2 II³--NeuAc-GgOse₃Cer - GM1 II³--NeuAc-GgOse₄Cer - 3-LM1 IV³--NeuAc-nLcOse₄Cer - 3-isoLMI IV³--NeuAc-LcOse₄Cer - Fuc-3-isoLMI IV³--NeuAc, III⁴-Fuc-LcOse₄Cer - GD1a IV³, II³--NeuAc₂-GgOse₄Cer - FAB-MS Fast atom bombardment-mass spectometry - GC-MS gas chromatography-mass spectometry Supported by NC1 RO1 CA11898 to Dr. Bigner and B8803X-00627-24B from the Swedish Medical Research Council to Dr. L. Svennerholm     

Verhaltensänderungen und bioelektrische Erscheinungen bei Mandelkernreizungen der Katze

Zusammenfassung Es wird über bioelektrische Verlaufsuntersuchungen bei Reizungen des basalen und lateralen Anteils des Mandelkerns der Katze und die dabei auftretenden Verhaltensänderungen berichtet.Die von Kaada als attention response bezeichnete Verhaltensänderung wurde auf Grund der bioelektrischen Befunde auf jene Zeit begrenzt, während der eine Depression der Spontanaktivität sowohl im Bereich des Cortex als auch des Subcortex nachweisbar war. Es ergab sich, daß lediglich das Sistieren der Bewegungen, das Kopfheben und Kopfvorstrecken sowie das Vor-sich-hinblicken zu dieser Reaktion zu zählen sind, während alle anderen Phänomene wie Kopf- und Blickwendung, Pupillenveränderungen usw. Symptome einer epileptischen Entgleisung darstellen.Mit 4 TextabbildungenMit Unterstützung durch die Deutsche Forschungsgemeinschaft.     

Ultrastructural studies of glycoconjugates in brain micro-blood vessels and amyloid plaques of scrapie-infected mice

Summary Lectin or glycoprotein-gold complexes and samples of scrapie-infected mouse brain embedded in Lowicryl K4M were used for ultrastructural localization of glycoconjugates. The lectins tested recognize the following residues: -D-galactosyl [RCA,Ricinus communis agglutinin (aggl.) 120], N-acetyl and N-glycolyl neuraminic acid (LFA,Limax flavus aggl.), N-acetyl-D-glucosaminyl and sialyl (WGA, Wheat germ aggl.), N-acetyl-D-galactosaminyl (HPA,Helix pomatia aggl., and DBA,Dolichosbiflorus aggl.), -D-mannosyl/-D-glucosyl (Con A, Concanavalin A), -D-galactosyl and -D-galactopyranoside (BSA,Bandeirea simplicifolia aggl., izolectin B₄). Labeling of the majority of micro-blood vessels (MBVs) located outside the plaque area and in the remaining cerebral cortex was similar to that which has been previously observed in non-infected animals. Some MBVs, however, located inside the plaque area and surrounded directly by amyloid fibers showed attenuation of the endothelium, the surface of which was scarcely and irregularly decorated with RCA, LFA, WGA and Con A. These abnormalities in the composition of glycoconjugates can be associated with previously noted increased permeability of some MBVs in the brains of scrapie-infected mice. Some vessels in the plaque area were encapsulated by perivascular deposits of homogenous or flocculogranular material containing several glycoconjugates. A very intimate structural relation between reactive (microglial-like) cells and amyloid fibers suggests the participation of these cells in elaboration of plaque material. Labeling of the cell surface and adjacent amyloid fibers with the same lectins (RCA, WGA, DBA, Con A) suggests the possibility that the glycosylation of these fibers occurs extracellularly. Only WGA and DBA were occasionally labeling some Golgi elements of the reactive cells.Supported in part by a grant from NINCDS No. 17271-06     

Lomest psychiatric case register: Old and new long-stay patients

Summary Data derived from a psychiatric case-register are presented on the attrition of the cohort of theold long-stay in-patients, and the accumulation of thenew long-stay cases in Lomest, a town in northern Italy, from 1975 to 1980. The characteristics of high user groups of out-patients attending the non-residential services are also described. The analysis seeks to provide some information on who has been left behind by the massive deinstitutionalization programme that has been carried out in Italy since 1970.     

Differential potentiation by calcium antagonists of neuromuscular blockade induced by pancuronium and succinylcholine in cats in vivo

Summary The effects of several calcium antagonists (verapamil, nicardipine and two diltiazem isomers, d-cis and l-cis diltiazem) alone and associated to non-depolarizing (pancuronium) and depolarizing (succinylcholine) neuromuscular blockers, were evaluated on sciatic nerve-tibialis anterior muscle preparations from cats in vivo. The calcium antagonists used (at 0.1 and 0.5mg/kg iv) did not modify the height of muscular twitches elicited indirectly. However, these agents potentiated in a dose-dependent way the neuromuscular blockade induced by iv pancuronium (2–40g/kg) and succinylcholine (6–200g/kg). The order of potency in increasing the effects of pancuronium was nicardipine d-cis diltiazem verapamil, whereas the order of potency in enhancing succinylcholine effects was d-cis diltiazem verapamil nicardipine. The effects of diltiazem were stereoselective, thus the potentiation induced by d-cis diltiazem was significantly greater in all cases than that induced by l-cis diltiazem, which suggests that calcium channel blockade plays a role in these interactions. However, other mechanisms such as calcium antagonists-induced nicotinic receptor desensitization may also be involved.     

Zur Bedeutung der γG-Globulinfraktion im Hirngewebe bei der subakuten sklerotisierenden Leukoencephalitis

Zusammenfassung Im Vergleich zu 10 Kontrollen wurde im Gehirngewebsextrakt der weißen wie auch der grauen Gehirnsubstanz bei 5 Patienten mit subakuter sklerotisierender Leukoencephalitis immunoelektrophoretisch die eindeutige Vermehrung der G-Globuline festgestellt. Im Extrakt aus der Gehirnsubstanz konnte dabei die Verdoppelung der G-Globulin-Präcipitationslinie wie auch die Verstärkung und Verlängerung dieser Eiweißfraktion im anodischen Gebiet beobachtet werden. Es wurde die Möglichkeit, die Befunde zu erklären, kurz diskutiert.

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Summary Extracts from white and grey matter of the brain were submitted to immunoelectrophoresis. Considerable increases of the gamma-G-globulin fractions were found in extracts from brains of 5 patients with subacute, sclerosing leuco-encephalitis as compared to 10 controls. A doubling of the gamma-G-globulin precipitation line could be observed as well as an increase and extension toward the anodic region. Possible explanations for these findings are discussed.

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Die Nomenklatur G-Globuline wurde im Sinne des Entwurfes der World Health Organisation (Prag 1964) angewendet und ist dem Begriff der 7 S -Globuline, der ₂-Globuline wie auch der _ss-Globuline gleich. So wurden die anderen zwei Immunoglobuline A- und M-Globulin benannt.     

Canine α-l-fucosidosis: A storage disease of Springer Spaniels

Summary Progressive ataxia, proprioceptive deficits, dysphagia and wasting occurred in a female and a male from the same litter of Springer Spaniels after the age of 12 and 19 months. At autopsy both showed marked enlargement of cranial parts of vagus and cervical nerves and dorsal root ganglia, and there was widespread vacuolation of cells of central nervous system (CNS), some peripheral nerves and of epithelial and mesenchymal cells of many organs; these vacuoles were largely empty in histological material, and were assumed to be of lysosomal origin after electronmicroscopic study. Cultured fibroblasts and peripheral blood leucocytes from the male were shown to be severely deficient in -l-fucosidase, and the mother of these cases was found to have less than half the expected activity of this enzyme in blood leucocytes. This condition is presented as a potential animal model of human -l-fucosidase.     

Hyperkinetic children: Early indicators of potential school failure

Hyperkinetic children are identified as a population-at risk upon admission to kindergarten. The etiology of hyperkinetic behavior is controversial. Organic driveness, hyperkinetic behavior disorder, postencephalitic behavior, brain damage with behavioral and conceptual deficit, Strauss syndrome, have all been used to label essentially similar symptom constellations. Bypassing the area of controversy, a study is reported that demonstrates that children who were identified as hyperkinetic (using behavioral criteria developed in an earlier study) were (1) absent from school more frequently, and (2) did remarkably less well on standardized tests of school readiness than their peers rated nonhyperkinetic. The implications are discussed and suggestions made for the development of intervention programs.An earlier version of this paper was presented at the Annual Meeting of the American Orthopsychiatric Association, March, 1967.     

Ultrastructural studies of concanavalin A receptors and 5′-nucleotidase localization in normal and injured mouse cerebral microvasculature

Summary Plant lectin concanavalin A conjugated with ferritin (Con A-F) injected i.v. was used for the detection of the specific monosaccharide residues (-d-mannosyl and -d-glucosyl) on the luminal surface of endothelial cells (ECs) in brain micro-blood vessels (MBVs). Both normal mice and animals with mechanically damaged blood-brain barrier (BBB) were used in this study. In addition, the activity of 5-nucleotidase (5N), the putative receptor for Con A, was studied cytochemically.Various methodologic experiments indicated that the reaction product formed on the luminal plasmalemma of ECs after incubation of samples in the cytochemical medium for the detection of 5N activity results from the action of unspecific phosphatase hydrolyzing both specific and nonspecific substrates. The abluminal side of the wall of MBVs seems to be a major location of 5N activity. Thus, no correlation between cytochemically demonstrable 5N activity and Con A receptor sites on the luminal surface of ECs was noted.After damage of the BBB, extensive internalization of the luminal plasmalemma forming the limiting membranes of pinocytotic vesicles, vacuoles, and endothelial channel-like structures was observed. This process was represented by a relatively rapid translocation of Con A receptors from luminal surface into the interior of the ECs and to the abluminal side of the vessel wall.Abbreviations AP Alkaline phosphatase - 5N 5-nucleotidase phate - AMP adenosine 5-monophosphate - CMP cytidine 5-monophosphate - GMP guanosine 5-monophosphate - UMP uridine 5-monophosphate - Con A concanavalin A - BBB blood-brain barrier - EC endothelial cell - HRP horseradish peroxidase - MBVs micro-blood vessels - NDPase nucleoside diphosphatase Supported in part by a grant from NINCDS No.17271-03     

Comparison of integrin adhesion molecules expressed by primary brain lymphomas and nodal lymphomas

The expression of 17 adhesion molecules was immunohistochemically examined in 5 primary cerebral lymphomas (PCL) and in 5 histologically similar nodal lymphomas (NL) to evaluate their possible involvement in selective targeting of lymphoma cells to the brain. PCL and NL tumor cells showed very similar expression patterns: they were consistently positive for ₃, ₄ and ₁ integrin chains; negative for ₂, ₆, ₃ and ₄ integrin chains; and heterogeneous for ₅, _L, _M, _X, ₂ and ₇ integrin chains, as well as for intercellular adhesion molecule-1 (ICAM-1) and the selectin LECAM-1. Loosely infiltrating PCL showed lower levels of the _L2 integrin than compact cell clusters. Vessels stained for ICAM-1 and vascular cell adhesion molecule-1 (VCAM-1). We conclude that the adhesion molecules implicated in the extravasation of non-neoplastic leukocytes (₄₁/VCAM-1 and _L2/ICAM-1) are also expressed by both PCL and NL. The adhesion molecules examined are apparently not selective mediators of lymphoma cell homing to the brain, but at least _L2 integrin might be related to the infiltration pattern of PCL within the brain parenchyma.Supported by the Sander Foundation